BACKGROUND
over millions of years of evolutionary time, living creatures from primitive cells to multi-cellular organisms must have been subjected to frequent episodes of dehydration; for example, bdelloid rotifers  adapt to desiccation by contracting into a compact shape and staying dormant until conditions improve  <cit> ; nematodes accumulate trehalose, a non-reducing sugar, to protect membranes and proteins from desiccation  <cit> ; plants express late embryogenesis abundant  proteins in maturing seeds and pollen in response to desiccation  <cit> .
the adaptability of organisms in response to dehydration through a state of suspended metabolism is essential for long-term survival  <cit> .
dehydration may be a selective force in evolution.
here, we report for the first time, the identification of cells that form tubular structures in response to stress.
these transformed cells have been termed straw cells based on their overall tubular morphology and ability to re-hydrate and form normal cells again.
although the desiccation of mammalian cells has been included in research by various groups in studies on the mechanisms of cellular response to low moisture  <cit> , tubular forms of mammalian cell response to dehydration have not been reported.
this lack of detection may be due to the invisibility of the straw cells in aqueous solution, and because sugars and salts added to cell culture for manipulation of the osmotic environment inhibit transformation to a tubular form.
RESULTS
existence of straw cells in tissues and in cultures
a wide range of tissue types and cell lines from different mammals have been surveyed for the existence of straw cells.
freshly harvested tissues of brain, heart, liver, lung and skin of young cows, and frozen tissues of normal and tumor sections of mouse prostate have straw cells in their native environments .
tubular structures in the hundreds were identified from  <dig> mg of brain and heart tissues, and in the tens of thousands from liver, lung and skin tissues.
approximately  <dig> straw cells/μl of tissue wash fluid  were quantified from bovine lung tissues .
in experiments with cultured cells, human mcf <dig>  caco <dig>  thp- <dig> and mouse d <dig> cells formed similar tubular shapes when dehydrated .
initially, very fine needle-like structures that we have termed filaments protrude from the cell surface.
these filaments continue to elongate and fuse with filaments from other dehydrated cells forming an integrated network.
the cell body itself becomes much smaller and assumes a tube-like structure.
cells that are detachable and mobile can cooperate in a coordinated manner by forming collaborative networks to acquire and distribute water may have increased their chances for survival.
the timing of transformation varies in vitro, with the majority of structures becoming visible at complete dehydration.
typically, more than 80% of cells transform with a population of  <dig>  cells in  <dig>  ml medium per well.
cell density, salts, the volume of the medium and drying rate affect the amount of transformation and filamentous growth.
cells dehydrated in a  <dig> × volume cell free phosphate saline medium and subjected to the same dehydration conditions produce no tubular structures.
this suggests a nutritional requirement for negating transformation.
because the transformation mechanism appears to be conserved across mammalian cell types to include differentiated macrophage  and adipose cells , it is reasonable to consider that dehydration exhibited a selective pressure on primitive cells.
cells that are detachable and mobile can cooperate in a coordinated manner by forming collaborative networks to acquire and distribute water may have increased their chances for survival.
sem images of straw cells and filamentous networks in solution are shown in figure 1c.
the filaments are spread out and connected to form networks, they originate from the tubular center, and the joints of the connections appear to be smooth and seamless.
cross-sections of the straw cells are shown in tem images .
the samples were prepared from dehydration-transformed cells that were precipitated at  <dig>  g, depending on the length of filamentous extensions; straw cells were either in the pellet or in the supernatant.
the central tubular wall has a thickness of  <dig> nm; thirty times thicker than the lipid bilayer of a normal cell membrane.
the wall structure appears dense and compact, and stained lightly with regular 1% osmium oxide fixation.
the filamentous extension's wall is approximately  <dig> nm thick,  <dig> nm thinner than the central tubular wall.
unlike the tubular center, the filamentous extensions have a nearly perfect homogeneous content and no recognizable organelles.
the volume of a tube is much smaller than that of the main cell body, indicating that most of the cellular material has been condensed.
filaments, typically between  <dig> and  <dig> μm in diameter, often extend far from the location of the main cell body.
in one instance, we observed filament growth to lengths of over  <dig> cm, an increase in approximately two thousand fold of the original length of the cell and seemingly confined only by the culturing well.
filaments were extended in multiple directions from cells along the culture flask as well as through the air.
tem images show the straw cell wall to be markedly robust, which probably indicates a state of dormancy and prevention of water loss.
straw cell properties
time course studies from four young animals revealed that straw cell population increases with the age of the animal in heart and lung tissues, but stays constant for brain, liver, and skin tissues .
when tissues post mortem were dehydrated in air, the straw cell population increased in brain and heart tissues.
brain tissues, when dehydrated for three days, produced straw cells comparable in number to those of liver and lung tissues at the initial stage of transformation .
on average the transformation from normal cells to a tubular structure occurs over an  <dig> h period.
a lethal dose of uv-c radiation  did not affect tubular transformation of cultured cells  or in postmortem tissues .
uv-c radiation also seems to have no effect on straw cell reversion to a normal round state .
during hydration, water passes rapidly through the straw cell network.
water movement through the straw cell network was estimated on a sub-second scale .
tubular structures from different cell types were connected to each other .
normal cells stained positively for actin and nucleic acids , whereas early tubular cell bodies were barely stainable and negative for mature straw cells and filaments .
the tubular wall appeared to be impermeable to small molecules such as ethanol, paraformaldehyde and tritonx- <dig> used in the staining procedure.
when rehydrated, filaments quickly disintegrate.
figure 2f, left bottom, displays collapsed filaments stained with rabbit straw cell polyclonal antibody.
collapsed filaments in solution produced numerous round shaped dots similar in size to large as e. coli cells.
antibodies generated against purified straw cells have produced positive signals from human urine but not feces .
transformed cells obtained from non-transformed cells in vitro were re-plated in fresh medium in new 4-chambered-wells.
more than 50% of the straw cells regained their normal spherical shape and began to divide in  <dig> –  <dig> days .
newly recovered cells were still resistant to staining indicating that they were still in a stressed state.
the morphologies of these recovering structures are presented in figure  <dig>
purified filaments were isolated from media and separated from lipid and protein fractions.
the filaments were laid down on a glass slide for viewing with some strands being measured up to  <dig> cm in length .
morphologically, the surface of the filaments is characterized by numerous hair-like structures and small circular openings .
interestingly, the structures are somewhat similar to that of hairy roots from a plant whose purpose is to absorb water and nutrients.
the cycle of dehydration and rehydration is characterized in figure  <dig>  when rehydrated, straw cells became visible and attached to the plate bottom in  <dig> days.
there are dark, irregular shaped bodies  that give rise to round-shaped cells in  <dig> to  <dig> days with different morphology.
dot-shaped particles with a dimension of  <dig> μm  enlarged to  <dig> μm size in  <dig> to  <dig> days.
some cells appeared to recover more readily than others with a more robust surface structure than cells in the panel to the right, which took a longer period of time for recovery.
cells of different dimensions developed from the matrix over the course of  <dig> days .
when recovering cells reached a diameter of approximately  <dig> μm, the overall cell morphology assumed a normal non-dehydrated appearance.
seventeen days later, they were indistinguishable from normal cells .
the dehydration-rehydration transformation cycle is summarized in figure 3b.
we repeated this 30-day cycle for several months and observed that cells were able to cycle back and forth between the straw cell and normal morphologies in response to dehydration and rehydration, respectively.
however, the number of total viable cells diminished with each successive cycle.
chemical compositions of the filaments
fourier-transform infrared spectroscopy  was used to examine the chemical composition of the filaments.
proteins and carbohydrates absorb infrared radiation and the intensity and characteristic bands provide the fingerprint of these molecules  <cit> .
alterations in individual vibrational modes and changes in coupled vibrations can be used to assess hydrogen bonding among proteins and carbohydrates  <cit> .
in the filaments, several bands have been shifted relative to the control spectra of proteins .
in the fingerprint region of  <dig> –  <dig> cm- <dig>  common bands can be seen between test samples and the controls around  <dig> cm- <dig>   <dig> cm- <dig> and  <dig> cm- <dig>  bands assigned to hydroxyl stretching modes  in the protein control samples  were decreased in intensity and shifted to higher frequencies  for peaks in the same range in the test samples, which is possibly due to disrupted hydrogen bonding in the test samples.
amide i band vibrations  were shifted to lower frequencies in the test samples, while the ch <dig> stretching modes  <dig> cm-1) appear sharper in both the absorbance spectra of the straw cells  and the blue dextran , but broader in the spectra of the protein controls.
this disparity suggests that the straw cells could contain larger amounts of carbohydrates compared to the controls.
these effects mimic those of hydrated trehalose  <cit> .
taken together, ftir recorded on caco <dig> and bovine straw cells, along with protein  and polysaccharide  standards indicate that elevated carbohydrate levels most likely contribute to the chemical composition of the straw cells.
protein composition of the filaments was estimated on sds/page.
collapsed tube separation on sds/page showed that approximately 1%  consisted of protein .
two bands with the molecular weight of approximately  <dig> kd, along with a bsa band at  <dig> kd were observed.
bsa appeared to be purified by a factor of  <dig>  fold when compared to the initial medium having a 10% fetal bovine serum .
the protein bands were processed by the in-gel tryptic digestion procedure and micro-sequenced.
among the proteins identified from these two bands using the data dependent acquisition method was a human 40s ribosomal protein .
western analysis of collapsed straw cells on sds/page revealed a single band around  <dig> kd .
mass spectrometry analysis of partially hydrolyzed filaments revealed a series of six glucose polymers; sulphated glucose polymers and n-acetylglucosamines polymers were among the polymers identified .
the polysaccharides were highly acidic and carried multiple negative charges at ph  <dig> .
the conditions favoring singly charged ions were optimized for detection in both positive and negative ion modes.
three linear polymers differ from each other by a glucose unit  and a fucose .
a glcnac  monomer was seen in  <dig> n hcl hydrolyzed bovine liver filaments .
among identified monomers, fucose  may be involved in branching.
n-acetylglucosamines is a common unit at the reducing end of the bi-antennary structures.
three linear glucose polymers from tubular caco <dig> cells differed by a neutral loss of sulphated glucose  as displayed in figure 5b.
serial-a sugar ions appear to be the oxygenated form of serial-b sugar ions and serial-c sugar ions were shown to carry two negative charges.
these polysaccharides can be summarized in the following structure: r <dig> and r <dig> attached to c <dig> .
the c <dig> and c <dig> of the glucose can be present either individually or together and was found in a range of just a few to over a million, when estimated by a gel filtration experiment .
the acidic makeup of straw cells causes them to be highly hydrophilic.
this is the probable reason for their presence in the supernatant of sequential treatment of  centrifugation at  <dig>  g;  chloroform: methanol extraction;  c <dig> reverse-phase matrix binding,  100°c,  <dig> min heat treatment and  5%tca precipitation.
radioisotope-labeling
the radioisotope-labeling technique was used to determine if the straw cells were either a product of a metabolically active process involving active cellular growth or if they were a lifeless, physical process involving spontaneous polymerization of cellular materials.
radioisotope labeling of the growth medium using  glucose determined that the incorporation of 14c glucose was more prevalent for dehydrated cells than for normal growing cells, indicating an elevated energy need and increased carbohydrate content of the straw cells .
more 14c was also found in protein fractions from cultures with tubular transformations than from regular growth cultures, indicating that an active amino acid and/or protein metabolism is involved in the process.
overall, the tubular transformation process appeared to be more active metabolically than for normal growth.
the lipid-phase is the bottom fraction from the chloroform:methanol extraction of the cells.
the inter-phase contains cell debris and proteins, and the tca fraction contains proteins from precipitation of the aqueous fraction.
the ethanol fraction contains carbohydrates from the remaining aqueous fraction in  <dig> volumes of ice-cold ethanol incubated at -20°c over night.
the remaining water-soluble fraction contains unused 14c-glucose.
collapsed filaments found in urine
the hplc method was used to analyze urinary samples from people at different ages for total carbohydrate quantification.
information on urination volume and time lapse from last urination was collected and used to calculate the carbohydrate production per hour per person, which was in turn converted to number of straw cell structures, based on the equivalency of the carbohydrate mass per tubular structure.
urine carbohydrate levels were found to fluctuate before and after meals, but the basal carbohydrate level remained stable, suggesting that it may be proportional to the straw cell wall material secreted in urine.
we discovered that the basal carbohydrate level  plotted against age; a polynomial correlation  between tubular cell production and human ages ranged from  <dig> to  <dig> years old .
urinary glycosaminoglycans  found widely in animal urine at levels possibly associated with diseases having repeated units of sulphated glucose  <cit> , may be derived from these tubular straw cell structures which contain sulphated glucose polymers.
because these filaments were visually detected in urine, the total urinary polysaccharide content may reflect the degree of straw cell formation inside the body, providing an indicator of the aging process.
discussion
thermodynamic and metabolic rates
critics have postulated that straw cell structures are the artifacts from dead cells, the polymerization of membrane systems, or growth of protein crystals.
assuming that is the case, then the conversion from a spherical to straw cell is a simple physical deformation process.
therefore, the free energy needed to maintain spherical and tubular structures, built from the same amount of biological material, can be estimated.
following the helfrich theory  <cit> , the equilibrium shape of a thin membrane covering the vesicle or emulsion droplet is determined by the minimization of the helmholtz free energy eh  of the system
eh=−Δpv+σa+∫da
mathtype@mtef@5@5@+=feaafiart1ev1aaatcvaufkttlearuwrp9mdh5mbpbiqv92aaexatlxbi9gbaebbnrfifhhdyfgasaach8aky=wiffydh8gipec8eeeu0xxdbba9frfj0=oqffea0dxdd9vqai=hguq8kuc9pgc9s8qqaq=dirpe0xb9q8qilsfr0=vr0=vr0dc8meaabaqaciaacagaaeqabaqabegadaaakeaacqwgfbqrdawgaawcbagaemisageabeaakiabg2da9iabgkhitiabgs5aejabdchawjabdafawjabgucarggaciab=n8azjabdgeabjabgucarmaapeaabagaemizaqmaemyqaekaei4was1aasaaaeaacqah6owaaeaacqaiyagmaaaaleqabeqdcqghrii8aogaeiikagyaasaaaeaacqaixaqmaeaacqwgsbgudawgaawcbagaegymaedabeaaaagccqghrawkdawcaaqaaiabigdaxaqaaiabdkfasnaabaaaleaacqaiyagmaeqaaaaakiabgkhitmaalaaabagaegomaidabagaemouai1aasbaasqaaiabicdawaqabaaaaogaeiykakyaawbaasqabeaacqaiyagmaagccqghrawkcqggoaakdawcaaqaaiqb=p7arzaaraaabagaemouai1aasbaasqaaiabigdaxaqabagccqwgsbgudawgaawcbagaegomaidabeaaaagccqggpaqkcqggdbqxaaa@5aea@
the first term in eq.
is given by the pressure difference across the membrane Δp and the volume of the droplet v, while the second term is determined by the interfacial tension σ and surface area a. the integral term in eq.
is often known as the free bending energy, where r <dig> is the spontaneous radius of curvature, κ and κ¯
mathtype@mtef@5@5@+=feaafiart1ev1aaatcvaufkttlearuwrp9mdh5mbpbiqv92aaexatlxbi9gbaebbnrfifhhdyfgasaach8aky=wiffydh8gipec8eeeu0xxdbba9frfj0=oqffea0dxdd9vqai=hguq8kuc9pgc9s8qqaq=dirpe0xb9q8qilsfr0=vr0=vr0dc8meaabaqaciaacagaaeqabaqabegadaaakeaaiigacuwf6owagaqeaaaa@2e7d@ is the mean and gaussian curvature elastic constants, respectively.
for a spherical structure, the two primary radii of curvature r <dig> = r <dig> = r, and the first two terms in eq.
are cancelled, so we have
eh−spherical=8πκ2+4πκ¯,
mathtype@mtef@5@5@+=feaafiart1ev1aaatcvaufkttlearuwrp9mdh5mbpbiqv92aaexatlxbi9gbaebbnrfifhhdyfgasaach8aky=wiffydh8gipec8eeeu0xxdbba9frfj0=oqffea0dxdd9vqai=hguq8kuc9pgc9s8qqaq=dirpe0xb9q8qilsfr0=vr0=vr0dc8meaabaqaciaacagaaeqabaqabegadaaakeaacqwgfbqrdawgaawcbagaemisagkaeyoei0iaem4camnaemicaanaemiaagmaemyzaumaemocainaemyaakmaem4yammaemyyaemaemibawgabeaakiabg2da9iabiida4ggaciab=b8awjab=p7arjabcicaoiabigdaxiabgkhitmaalaaabagaemouaifabagaemouai1aasbaasqaaiabicdawaqabaaaaogaeiykakyaawbaasqabeaacqaiyagmaagccqghrawkcqai0aancqwfapaccuwf6owagaqeagqaciab+xcasaaa@5039@
for a tubular structure with the inner radius a, outer radius b and length l, r <dig> =  <dig>  we have
eh−tubular=πσl+πκl+8πκ¯,
mathtype@mtef@5@5@+=feaafiart1ev1aaatcvaufkttlearuwrp9mdh5mbpbiqv92aaexatlxbi9gbamxvp5wqsxmqhnxajn0bkvguhdwzzbqegyvzyrwyufgarqqtubsr4rnchbgeagqia8vkikvafgielifelkfelk=iy=hhbbf9v8qqaqfr0xc9pk0xbba9q8wqffeay=bilkvclq=jhqvepeea0=as0db9vqpepesp0xe9fve9fve9gapdbaqaaegacagaaiaabeqaamqadiabaagcbagaemyrau0aasbaasqaaiabdieaijabgkhitiabdsha0jabdwha1jabdkgaijabdwha1jabdygasjabdggahjabdkhaybqabagccqgh9aqpiigacqwfapaccqwfdpwccqwgmbatcqggoaakcqwghbqycqghrawkcqwgibgycqggpaqkcqggbbwwcqaiyagmcqghsisldawcaaqaaiabcicaoiabdkgaijabgkhitiabdggahjabcmcapmaacaaaleqabagaegomaidaaagcbagaemyyaemaemoyaigaaiabc2fadjabgucariab=b8awjab=p7arjabdyeamjabcicaomaalaaabagaegymaedabagaemyyaegaaiabgucarmaalaaabagaegymaedabagaemoyaigaaiabcmcapiabgucariabiida4iab=b8awjqb=p7arzaaraacdigaa4hlaaaa@74dd@
from literature, the κ and κ¯
mathtype@mtef@5@5@+=feaafiart1ev1aaatcvaufkttlearuwrp9mdh5mbpbiqv92aaexatlxbi9gbaebbnrfifhhdyfgasaach8aky=wiffydh8gipec8eeeu0xxdbba9frfj0=oqffea0dxdd9vqai=hguq8kuc9pgc9s8qqaq=dirpe0xb9q8qilsfr0=vr0=vr0dc8meaabaqaciaacagaaeqabaqabegadaaakeaaiigacuwf6owagaqeaaaa@2e7d@ of the lipid bilayers are in the range of  × 10- <dig> j , as a result, eq.
yields eh~10-18-10- <dig> j per spherical cell.
these values for carbohydrates, which are the major components of the straw cell wall, are not available.
from the tem measurements, the spherical cell has a typical radius r =  <dig> μm while the straw cell filaments, has a length of  <dig> cm, or  <dig>  ×  <dig> μm, an inner radius a =  <dig>  μm and an outer radius b =  <dig>  μm .
it is immediately noted that the exceptionally large aspect ratio  of the straw cell causes the second term in eq.
to dominate any other term in eq.
and  containing κ and κ¯
mathtype@mtef@5@5@+=feaafiart1ev1aaatcvaufkttlearuwrp9mdh5mbpbiqv92aaexatlxbi9gbaebbnrfifhhdyfgasaach8aky=wiffydh8gipec8eeeu0xxdbba9frfj0=oqffea0dxdd9vqai=hguq8kuc9pgc9s8qqaq=dirpe0xb9q8qilsfr0=vr0=vr0dc8meaabaqaciaacagaaeqabaqabegadaaakeaaiigacuwf6owagaqeaaaa@2e7d@.
in addition, the first term in eq.
always contributes accumulatively to the shape energy.
considerable free energy, mainly in the form of the elastic energy, is needed to account for the remarkable spherical-to-tubular shape transformation, with the cell volume increased from  <dig>  ×  <dig> to  <dig>  ×  <dig>  and the cell surface area increased from  <dig>  ×  <dig> to  <dig>  ×  <dig> .
we conclude that the tubular structure, as compared to the spherical cell, is heavily disfavored in free energy; which leads us to believe that the spontaneous polymerization of dead cell matrix to tubular structure is an unlikely event.
in reality, the straw cells cannot be simplified to a rod-shaped structure with an overall uniform composition.
not only do they have microscopic hair-like structures covering the surface , but they also have differences in composition from the tubular center to the filamentous extensions  that makes a uniformity assumption untenable.
during the spherical to tubular shape transformation, we observed changes in cell volume, surface area, and cell surface composition.
the biological transformation we describe differs from a physical event where energy and material exchanges occur throughout the process.
during the reversion of a straw cell to a normal round cell, the tubular center , houses organelles and grows by enlargement perpendicular to the elongated cell wall  into a regular round shaped cell.
cellular metabolic rates are determined by the diffusion of ions and biomolecules  <cit>  and are expected to be much slower in straw cells than spherical cells because of the narrow cylindrical geometry restricting the intracellular diffusion of solutes compared to a round shaped geometry  <cit> .
the diffusion coefficient of k+ in the t-tubules of skeletal muscle fibers is anomalous and 27% less than its value in free solution  <cit> .
we also observed a much slower growth rate in straw cells  during reversion to regular sized cells, while normal unstressed spherical cells take  <dig> days to duplicate.
it is unclear how straw cells resume a normal round cellular morphology.
it is also uncertain as to how ion channels operate during straw cell development.
straw cell filaments have an outer diameter from  <dig> to  <dig> μm  and appear to have little cytoplasm .
this is in contrast to fungal apical growth where the elongation of hyphae is typically characterized with a much greater amount of cytoplasm and a distinct endoplasmic reticulum that consists of a network of tubules connected to the nuclear envelope  <cit> .
cell shape in bacteria is often defined by the distinct presence of peptidoglycan, a complex polymer built with glycan chains that are interconnected via peptide crossbridges  <cit> .
cells with a more complex shape, such as rod-shaped cells, exhibit an additional growth mode responsible for cell elongation  <cit> .
it is unknown if straw cell assembly in regard to the cell wall is similar to bacteria, but glycoproteins and sulphated glucose polymers are primary constituents of the straw cell wall.
indeed, straw cells can be independently observed in a  <dig> min experiment.
this simply involves collecting any mammalian tissue fluid, placing  <dig> μl on a glass slide, and observing the droplet under a light microscope.
as the droplet dries, the existence of straw cells and their connected filament networks are readily seen .
proposed model of transformation
we propose that water activity sensors, present on the surface of mammalian cells, survey the hydration status of the environment and may be a type of membrane bound protein kinase.
in plants, mitogen-activated protein  kinases  <cit>  and phospohlipase d  <cit>  have been upstream responders to the drought stress signaling pathway in arabidopsis.
a study of osmotic-stress-related proteins in rice has identified  <dig> specific proteins including kinases  <cit> .
water sensing may be a conserved mechanism throughout eukaryotes and mammalian cells may use similar map kinases for intracellular signaling.
these sensors, when triggered, invoke a signaling cascade resulting in stress related transcriptional activity in the nucleus.
as a result, we postulate that in mammalian cells, one of the potential protective responses involves a dramatic change in cell morphology resulting in the formation of straw cells.
fragmentation of the caco- <dig> nucleus , along with a synthesis of tubular wall was observed during the straw cell transformation process.
the time-lapse images were obtained over the entire dehydration process using light microscopy and tem.
these images reveal the presence of polymers assembled along the nuclear membrane .
these subunits are hypothesized to be the building material for the tubular cell wall, presumably, after they have cross-linked to each other.
in an attempt to identify the presence of the surface water activity sensors and subsequent proteins involved in the signal cascade, we used small molecules to inhibit straw cell transformation.
initial results indicated that this process could be manipulated and inhibited with naturally occurring compounds as well as synthetic compounds.
for example, changes in membrane fluidity by salts and sugars  disrupt the tubular transformation; antibiotics  that inhibit protein synthesis interfered with the tubular transformation by producing filaments that were somewhat truncated.
implication in human diseases
the large quantities of straw cells and their ubiquitous nature make them a potential unifying factor across a diversity of age related diseases.
the conversion of cells into straw cells may be involved in the initial onset and progression of these diseases, the causes of which are still unknown.
moreover, straw cell formation may be a common physiological response in various types of human degenerative disease.
another area of human health where this phenomenon may play a role is tumor development and proliferation.
the hydrophilic, mobile, detachment of straw cells may be a key component of metastasis.
as such, hydrophilic straw cells from cancer cells may possibly move around in extracellular fluid and find new locations to grow.
there are many unanswered questions regarding the composition of these tubular cell structures found in a variety of mammalian tissues.
for example, what suite of genes encodes the instructions governing the assembly of these tubular structures?
what are the necessary molecules for making "unions" and "tees" in the filaments so as to form straw cell networks?
is straw cell transformation a conserved mechanism that mammalian cells use in response to the stress of dehydration and perhaps other stress inducing environmental factors?
what is the physiological role of straw cell formation in vivo?
how much dehydration occurs inside the body either locally or systemically?
because the cellular transformation is reproducible in vitro in a 96-well plate, screening chemical libraries for inhibitory compounds to filamentous transformation is feasible and may result in the ability to control straw cell development in vivo.
this may have implications in mediating degenerative diseases and tumor proliferation.
for example, an in vitro assay using azithromysin at  <dig> ppm resulted in mammalian straw cells with both smaller straw cells and shortened filaments .
one type of strategy could include selectively inhibiting protein kinases on the cell surface desensitizing the stress surveillance mechanism.
CONCLUSIONS
several factors bolster our hypothesis that these tubular structures are indeed special cellular structures that form when a given cell adapts to stress rather than formed from either artifacts or from spontaneous polymerization.
these factors include:  the pre-existence of tubular structures in all of our examined tissues;  the ability to observe filamentous structures via sem, tem and light microscopy; the presence of hair-like extensions and small pores or openings on the fixed straw cells  the non-production of straw cells in cell-free medium with reagents that changed osmotic potential ;  the prohibition of spontaneous conversion from sphere-to-straw cells by free energy;  the radioisotope labeling of growth medium, showing the transformation to be a metabolically active process;  the growth of straw cells into normal cells capable of dividing;  the production of truncated straw cells, caused by the interference of antibiotics inhibiting protein synthesis in bacteria;  the discovery that tubular walls are made of sulphated glucose polymers after purifying straw cells in gram quantity, and subjecting them to ftir and mass spectrometry analysis.
we propose to call these tubular structures transformed through dehydration, "straw cells" because the filaments they produce appear to act as a conduit for the transport of water much like a drinking straw.
similar to the fungal spores, the straw cells are produced by a survival mechanism to protect them from stressful conditions and then revert to a normal morphology when the environment becomes favorable.
understanding the function of these straw cells and developing methods to interrupt their production is may elucidate the cause and effect of the basic pathogenesis in degenerative diseases including malignant tumor metastasis.

 over millions of years of evolutionary time, living creatures from primitive cells to multi-cellular organisms must have been subjected to frequent episodes of dehydration; for example, bdelloid rotifers adapt to desiccation by contracting into a compact shape and staying dormant until conditions improve; nematodes accumulate trehalose, a non-reducing sugar, to protect membranes and proteins from desiccation; plants express late embryogenesis abundant proteins in maturing seeds and pollen in response to desiccation. the adaptability of organisms in response to dehydration through a state of suspended metabolism is essential for long-term survival. dehydration may be a selective force in evolution. here, we report for the first time, the identification of cells that form tubular structures in response to stress. these transformed cells have been termed straw cells based on their overall tubular morphology and ability to re-hydrate and form normal cells again. although the desiccation of mammalian cells has been included in research by various groups in studies on the mechanisms of cellular response to low moisture, tubular forms of mammalian cell response to dehydration have not been reported. this lack of detection may be due to the invisibility of the straw cells in aqueous solution, and because sugars and salts added to cell culture for manipulation of the osmotic environment inhibit transformation to a tubular form.  existence of straw cells in tissues and in cultures a wide range of tissue types and cell lines from different mammals have been surveyed for the existence of straw cells. freshly harvested tissues of brain, heart, liver, lung and skin of young cows, and frozen tissues of normal and tumor sections of mouse prostate have straw cells in their native environments. tubular structures in the hundreds were identified from mg of brain and heart tissues, and in the tens of thousands from liver, lung and skin tissues. approximately straw cells/μl of tissue wash fluid were quantified from bovine lung tissues. in experiments with cultured cells, human mcf caco thp- and mouse d cells formed similar tubular shapes when dehydrated. initially, very fine needle-like structures that we have termed filaments protrude from the cell surface. these filaments continue to elongate and fuse with filaments from other dehydrated cells forming an integrated network. the cell body itself becomes much smaller and assumes a tube-like structure. cells that are detachable and mobile can cooperate in a coordinated manner by forming collaborative networks to acquire and distribute water may have increased their chances for survival. the timing of transformation varies in vitro, with the majority of structures becoming visible at complete dehydration. typically, more than 80% of cells transform with a population of cells in ml medium per well. cell density, salts, the volume of the medium and drying rate affect the amount of transformation and filamentous growth. cells dehydrated in a × volume cell free phosphate saline medium and subjected to the same dehydration conditions produce no tubular structures. this suggests a nutritional requirement for negating transformation. because the transformation mechanism appears to be conserved across mammalian cell types to include differentiated macrophage and adipose cells, it is reasonable to consider that dehydration exhibited a selective pressure on primitive cells. cells that are detachable and mobile can cooperate in a coordinated manner by forming collaborative networks to acquire and distribute water may have increased their chances for survival. sem images of straw cells and filamentous networks in solution are shown in figure 1c. the filaments are spread out and connected to form networks, they originate from the tubular center, and the joints of the connections appear to be smooth and seamless. cross-sections of the straw cells are shown in tem images. the samples were prepared from dehydration-transformed cells that were precipitated at g, depending on the length of filamentous extensions; straw cells were either in the pellet or in the supernatant. the central tubular wall has a thickness of nm; thirty times thicker than the lipid bilayer of a normal cell membrane. the wall structure appears dense and compact, and stained lightly with regular 1% osmium oxide fixation. the filamentous extension's wall is approximately nm thick, nm thinner than the central tubular wall. unlike the tubular center, the filamentous extensions have a nearly perfect homogeneous content and no recognizable organelles. the volume of a tube is much smaller than that of the main cell body, indicating that most of the cellular material has been condensed. filaments, typically between and μm in diameter, often extend far from the location of the main cell body. in one instance, we observed filament growth to lengths of over cm, an increase in approximately two thousand fold of the original length of the cell and seemingly confined only by the culturing well. filaments were extended in multiple directions from cells along the culture flask as well as through the air. tem images show the straw cell wall to be markedly robust, which probably indicates a state of dormancy and prevention of water loss. straw cell properties time course studies from four young animals revealed that straw cell population increases with the age of the animal in heart and lung tissues, but stays constant for brain, liver, and skin tissues. when tissues post mortem were dehydrated in air, the straw cell population increased in brain and heart tissues. brain tissues, when dehydrated for three days, produced straw cells comparable in number to those of liver and lung tissues at the initial stage of transformation. on average the transformation from normal cells to a tubular structure occurs over an h period. a lethal dose of uv-c radiation did not affect tubular transformation of cultured cells or in postmortem tissues. uv-c radiation also seems to have no effect on straw cell reversion to a normal round state. during hydration, water passes rapidly through the straw cell network. water movement through the straw cell network was estimated on a sub-second scale. tubular structures from different cell types were connected to each other. normal cells stained positively for actin and nucleic acids, whereas early tubular cell bodies were barely stainable and negative for mature straw cells and filaments. the tubular wall appeared to be impermeable to small molecules such as ethanol, paraformaldehyde and tritonx- used in the staining procedure. when rehydrated, filaments quickly disintegrate. figure 2f, left bottom, displays collapsed filaments stained with rabbit straw cell polyclonal antibody. collapsed filaments in solution produced numerous round shaped dots similar in size to large as e. coli cells. antibodies generated against purified straw cells have produced positive signals from human urine but not feces. transformed cells obtained from non-transformed cells in vitro were re-plated in fresh medium in new 4-chambered-wells. more than 50% of the straw cells regained their normal spherical shape and began to divide in – days. newly recovered cells were still resistant to staining indicating that they were still in a stressed state. the morphologies of these recovering structures are presented in figure purified filaments were isolated from media and separated from lipid and protein fractions. the filaments were laid down on a glass slide for viewing with some strands being measured up to cm in length. morphologically, the surface of the filaments is characterized by numerous hair-like structures and small circular openings. interestingly, the structures are somewhat similar to that of hairy roots from a plant whose purpose is to absorb water and nutrients. the cycle of dehydration and rehydration is characterized in figure when rehydrated, straw cells became visible and attached to the plate bottom in days. there are dark, irregular shaped bodies that give rise to round-shaped cells in to days with different morphology. dot-shaped particles with a dimension of μm enlarged to μm size in to days. some cells appeared to recover more readily than others with a more robust surface structure than cells in the panel to the right, which took a longer period of time for recovery. cells of different dimensions developed from the matrix over the course of days. when recovering cells reached a diameter of approximately μm, the overall cell morphology assumed a normal non-dehydrated appearance. seventeen days later, they were indistinguishable from normal cells. the dehydration-rehydration transformation cycle is summarized in figure 3b. we repeated this 30-day cycle for several months and observed that cells were able to cycle back and forth between the straw cell and normal morphologies in response to dehydration and rehydration, respectively. however, the number of total viable cells diminished with each successive cycle. chemical compositions of the filaments fourier-transform infrared spectroscopy was used to examine the chemical composition of the filaments. proteins and carbohydrates absorb infrared radiation and the intensity and characteristic bands provide the fingerprint of these molecules. alterations in individual vibrational modes and changes in coupled vibrations can be used to assess hydrogen bonding among proteins and carbohydrates. in the filaments, several bands have been shifted relative to the control spectra of proteins. in the fingerprint region of – cm- common bands can be seen between test samples and the controls around cm- cm- and cm- bands assigned to hydroxyl stretching modes in the protein control samples were decreased in intensity and shifted to higher frequencies for peaks in the same range in the test samples, which is possibly due to disrupted hydrogen bonding in the test samples. amide i band vibrations were shifted to lower frequencies in the test samples, while the ch stretching modes cm-1) appear sharper in both the absorbance spectra of the straw cells and the blue dextran, but broader in the spectra of the protein controls. this disparity suggests that the straw cells could contain larger amounts of carbohydrates compared to the controls. these effects mimic those of hydrated trehalose. taken together, ftir recorded on caco and bovine straw cells, along with protein and polysaccharide standards indicate that elevated carbohydrate levels most likely contribute to the chemical composition of the straw cells. protein composition of the filaments was estimated on sds/page. collapsed tube separation on sds/page showed that approximately 1% consisted of protein. two bands with the molecular weight of approximately kd, along with a bsa band at kd were observed. bsa appeared to be purified by a factor of fold when compared to the initial medium having a 10% fetal bovine serum. the protein bands were processed by the in-gel tryptic digestion procedure and micro-sequenced. among the proteins identified from these two bands using the data dependent acquisition method was a human 40s ribosomal protein. western analysis of collapsed straw cells on sds/page revealed a single band around kd. mass spectrometry analysis of partially hydrolyzed filaments revealed a series of six glucose polymers; sulphated glucose polymers and n-acetylglucosamines polymers were among the polymers identified. the polysaccharides were highly acidic and carried multiple negative charges at ph. the conditions favoring singly charged ions were optimized for detection in both positive and negative ion modes. three linear polymers differ from each other by a glucose unit and a fucose. a glcnac monomer was seen in n hcl hydrolyzed bovine liver filaments. among identified monomers, fucose may be involved in branching. n-acetylglucosamines is a common unit at the reducing end of the bi-antennary structures. three linear glucose polymers from tubular caco cells differed by a neutral loss of sulphated glucose as displayed in figure 5b. serial-a sugar ions appear to be the oxygenated form of serial-b sugar ions and serial-c sugar ions were shown to carry two negative charges. these polysaccharides can be summarized in the following structure: r and r attached to c. the c and c of the glucose can be present either individually or together and was found in a range of just a few to over a million, when estimated by a gel filtration experiment. the acidic makeup of straw cells causes them to be highly hydrophilic. this is the probable reason for their presence in the supernatant of sequential treatment of centrifugation at g; chloroform: methanol extraction; c reverse-phase matrix binding, 100°c, min heat treatment and 5%tca precipitation. radioisotope-labeling the radioisotope-labeling technique was used to determine if the straw cells were either a product of a metabolically active process involving active cellular growth or if they were a lifeless, physical process involving spontaneous polymerization of cellular materials. radioisotope labeling of the growth medium using glucose determined that the incorporation of 14c glucose was more prevalent for dehydrated cells than for normal growing cells, indicating an elevated energy need and increased carbohydrate content of the straw cells. more 14c was also found in protein fractions from cultures with tubular transformations than from regular growth cultures, indicating that an active amino acid and/or protein metabolism is involved in the process. overall, the tubular transformation process appeared to be more active metabolically than for normal growth. the lipid-phase is the bottom fraction from the chloroform:methanol extraction of the cells. the inter-phase contains cell debris and proteins, and the tca fraction contains proteins from precipitation of the aqueous fraction. the ethanol fraction contains carbohydrates from the remaining aqueous fraction in volumes of ice-cold ethanol incubated at -20°c over night. the remaining water-soluble fraction contains unused 14c-glucose. collapsed filaments found in urine the hplc method was used to analyze urinary samples from people at different ages for total carbohydrate quantification. information on urination volume and time lapse from last urination was collected and used to calculate the carbohydrate production per hour per person, which was in turn converted to number of straw cell structures, based on the equivalency of the carbohydrate mass per tubular structure. urine carbohydrate levels were found to fluctuate before and after meals, but the basal carbohydrate level remained stable, suggesting that it may be proportional to the straw cell wall material secreted in urine. we discovered that the basal carbohydrate level plotted against age; a polynomial correlation between tubular cell production and human ages ranged from to years old. urinary glycosaminoglycans found widely in animal urine at levels possibly associated with diseases having repeated units of sulphated glucose, may be derived from these tubular straw cell structures which contain sulphated glucose polymers. because these filaments were visually detected in urine, the total urinary polysaccharide content may reflect the degree of straw cell formation inside the body, providing an indicator of the aging process. discussion thermodynamic and metabolic rates critics have postulated that straw cell structures are the artifacts from dead cells, the polymerization of membrane systems, or growth of protein crystals. assuming that is the case, then the conversion from a spherical to straw cell is a simple physical deformation process. therefore, the free energy needed to maintain spherical and tubular structures, built from the same amount of biological material, can be estimated. following the helfrich theory, the equilibrium shape of a thin membrane covering the vesicle or emulsion droplet is determined by the minimization of the helmholtz free energy eh of the system eh=−Δpv+σa+∫da mathtype@mtef@5@5@+=feaafiart1ev1aaatcvaufkttlearuwrp9mdh5mbpbiqv92aaexatlxbi9gbaebbnrfifhhdyfgasaach8aky=wiffydh8gipec8eeeu0xxdbba9frfj0=oqffea0dxdd9vqai=hguq8kuc9pgc9s8qqaq=dirpe0xb9q8qilsfr0=vr0=vr0dc8meaabaqaciaacagaaeqabaqabegadaaakeaacqwgfbqrdawgaawcbagaemisageabeaakiabg2da9iabgkhitiabgs5aejabdchawjabdafawjabgucarggaciab=n8azjabdgeabjabgucarmaapeaabagaemizaqmaemyqaekaei4was1aasaaaeaacqah6owaaeaacqaiyagmaaaaleqabeqdcqghrii8aogaeiikagyaasaaaeaacqaixaqmaeaacqwgsbgudawgaawcbagaegymaedabeaaaagccqghrawkdawcaaqaaiabigdaxaqaaiabdkfasnaabaaaleaacqaiyagmaeqaaaaakiabgkhitmaalaaabagaegomaidabagaemouai1aasbaasqaaiabicdawaqabaaaaogaeiykakyaawbaasqabeaacqaiyagmaagccqghrawkcqggoaakdawcaaqaaiqb=p7arzaaraaabagaemouai1aasbaasqaaiabigdaxaqabagccqwgsbgudawgaawcbagaegomaidabeaaaagccqggpaqkcqggdbqxaaa@5aea@ the first term in eq. is given by the pressure difference across the membrane Δp and the volume of the droplet v, while the second term is determined by the interfacial tension σ and surface area a. the integral term in eq. is often known as the free bending energy, where r is the spontaneous radius of curvature, κ and κ¯ mathtype@mtef@5@5@+=feaafiart1ev1aaatcvaufkttlearuwrp9mdh5mbpbiqv92aaexatlxbi9gbaebbnrfifhhdyfgasaach8aky=wiffydh8gipec8eeeu0xxdbba9frfj0=oqffea0dxdd9vqai=hguq8kuc9pgc9s8qqaq=dirpe0xb9q8qilsfr0=vr0=vr0dc8meaabaqaciaacagaaeqabaqabegadaaakeaaiigacuwf6owagaqeaaaa@2e7d@ is the mean and gaussian curvature elastic constants, respectively. for a spherical structure, the two primary radii of curvature r = r = r, and the first two terms in eq. are cancelled, so we have eh−spherical=8πκ2+4πκ¯, mathtype@mtef@5@5@+=feaafiart1ev1aaatcvaufkttlearuwrp9mdh5mbpbiqv92aaexatlxbi9gbaebbnrfifhhdyfgasaach8aky=wiffydh8gipec8eeeu0xxdbba9frfj0=oqffea0dxdd9vqai=hguq8kuc9pgc9s8qqaq=dirpe0xb9q8qilsfr0=vr0=vr0dc8meaabaqaciaacagaaeqabaqabegadaaakeaacqwgfbqrdawgaawcbagaemisagkaeyoei0iaem4camnaemicaanaemiaagmaemyzaumaemocainaemyaakmaem4yammaemyyaemaemibawgabeaakiabg2da9iabiida4ggaciab=b8awjab=p7arjabcicaoiabigdaxiabgkhitmaalaaabagaemouaifabagaemouai1aasbaasqaaiabicdawaqabaaaaogaeiykakyaawbaasqabeaacqaiyagmaagccqghrawkcqai0aancqwfapaccuwf6owagaqeagqaciab+xcasaaa@5039@ for a tubular structure with the inner radius a, outer radius b and length l, r = we have eh−tubular=πσl+πκl+8πκ¯, mathtype@mtef@5@5@+=feaafiart1ev1aaatcvaufkttlearuwrp9mdh5mbpbiqv92aaexatlxbi9gbamxvp5wqsxmqhnxajn0bkvguhdwzzbqegyvzyrwyufgarqqtubsr4rnchbgeagqia8vkikvafgielifelkfelk=iy=hhbbf9v8qqaqfr0xc9pk0xbba9q8wqffeay=bilkvclq=jhqvepeea0=as0db9vqpepesp0xe9fve9fve9gapdbaqaaegacagaaiaabeqaamqadiabaagcbagaemyrau0aasbaasqaaiabdieaijabgkhitiabdsha0jabdwha1jabdkgaijabdwha1jabdygasjabdggahjabdkhaybqabagccqgh9aqpiigacqwfapaccqwfdpwccqwgmbatcqggoaakcqwghbqycqghrawkcqwgibgycqggpaqkcqggbbwwcqaiyagmcqghsisldawcaaqaaiabcicaoiabdkgaijabgkhitiabdggahjabcmcapmaacaaaleqabagaegomaidaaagcbagaemyyaemaemoyaigaaiabc2fadjabgucariab=b8awjab=p7arjabdyeamjabcicaomaalaaabagaegymaedabagaemyyaegaaiabgucarmaalaaabagaegymaedabagaemoyaigaaiabcmcapiabgucariabiida4iab=b8awjqb=p7arzaaraacdigaa4hlaaaa@74dd@ from literature, the κ and κ¯ mathtype@mtef@5@5@+=feaafiart1ev1aaatcvaufkttlearuwrp9mdh5mbpbiqv92aaexatlxbi9gbaebbnrfifhhdyfgasaach8aky=wiffydh8gipec8eeeu0xxdbba9frfj0=oqffea0dxdd9vqai=hguq8kuc9pgc9s8qqaq=dirpe0xb9q8qilsfr0=vr0=vr0dc8meaabaqaciaacagaaeqabaqabegadaaakeaaiigacuwf6owagaqeaaaa@2e7d@ of the lipid bilayers are in the range of × 10- j, as a result, eq. yields eh~10-18-10- j per spherical cell. these values for carbohydrates, which are the major components of the straw cell wall, are not available. from the tem measurements, the spherical cell has a typical radius r = μm while the straw cell filaments, has a length of cm, or × μm, an inner radius a = μm and an outer radius b = μm. it is immediately noted that the exceptionally large aspect ratio of the straw cell causes the second term in eq. to dominate any other term in eq. and containing κ and κ¯ mathtype@mtef@5@5@+=feaafiart1ev1aaatcvaufkttlearuwrp9mdh5mbpbiqv92aaexatlxbi9gbaebbnrfifhhdyfgasaach8aky=wiffydh8gipec8eeeu0xxdbba9frfj0=oqffea0dxdd9vqai=hguq8kuc9pgc9s8qqaq=dirpe0xb9q8qilsfr0=vr0=vr0dc8meaabaqaciaacagaaeqabaqabegadaaakeaaiigacuwf6owagaqeaaaa@2e7d@. in addition, the first term in eq. always contributes accumulatively to the shape energy. considerable free energy, mainly in the form of the elastic energy, is needed to account for the remarkable spherical-to-tubular shape transformation, with the cell volume increased from × to × and the cell surface area increased from × to ×. we conclude that the tubular structure, as compared to the spherical cell, is heavily disfavored in free energy; which leads us to believe that the spontaneous polymerization of dead cell matrix to tubular structure is an unlikely event. in reality, the straw cells cannot be simplified to a rod-shaped structure with an overall uniform composition. not only do they have microscopic hair-like structures covering the surface, but they also have differences in composition from the tubular center to the filamentous extensions that makes a uniformity assumption untenable. during the spherical to tubular shape transformation, we observed changes in cell volume, surface area, and cell surface composition. the biological transformation we describe differs from a physical event where energy and material exchanges occur throughout the process. during the reversion of a straw cell to a normal round cell, the tubular center, houses organelles and grows by enlargement perpendicular to the elongated cell wall into a regular round shaped cell. cellular metabolic rates are determined by the diffusion of ions and biomolecules and are expected to be much slower in straw cells than spherical cells because of the narrow cylindrical geometry restricting the intracellular diffusion of solutes compared to a round shaped geometry. the diffusion coefficient of k+ in the t-tubules of skeletal muscle fibers is anomalous and 27% less than its value in free solution. we also observed a much slower growth rate in straw cells during reversion to regular sized cells, while normal unstressed spherical cells take days to duplicate. it is unclear how straw cells resume a normal round cellular morphology. it is also uncertain as to how ion channels operate during straw cell development. straw cell filaments have an outer diameter from to μm and appear to have little cytoplasm. this is in contrast to fungal apical growth where the elongation of hyphae is typically characterized with a much greater amount of cytoplasm and a distinct endoplasmic reticulum that consists of a network of tubules connected to the nuclear envelope. cell shape in bacteria is often defined by the distinct presence of peptidoglycan, a complex polymer built with glycan chains that are interconnected via peptide crossbridges. cells with a more complex shape, such as rod-shaped cells, exhibit an additional growth mode responsible for cell elongation. it is unknown if straw cell assembly in regard to the cell wall is similar to bacteria, but glycoproteins and sulphated glucose polymers are primary constituents of the straw cell wall. indeed, straw cells can be independently observed in a min experiment. this simply involves collecting any mammalian tissue fluid, placing μl on a glass slide, and observing the droplet under a light microscope. as the droplet dries, the existence of straw cells and their connected filament networks are readily seen. proposed model of transformation we propose that water activity sensors, present on the surface of mammalian cells, survey the hydration status of the environment and may be a type of membrane bound protein kinase. in plants, mitogen-activated protein kinases and phospohlipase d have been upstream responders to the drought stress signaling pathway in arabidopsis. a study of osmotic-stress-related proteins in rice has identified specific proteins including kinases. water sensing may be a conserved mechanism throughout eukaryotes and mammalian cells may use similar map kinases for intracellular signaling. these sensors, when triggered, invoke a signaling cascade resulting in stress related transcriptional activity in the nucleus. as a result, we postulate that in mammalian cells, one of the potential protective responses involves a dramatic change in cell morphology resulting in the formation of straw cells. fragmentation of the caco- nucleus, along with a synthesis of tubular wall was observed during the straw cell transformation process. the time-lapse images were obtained over the entire dehydration process using light microscopy and tem. these images reveal the presence of polymers assembled along the nuclear membrane. these subunits are hypothesized to be the building material for the tubular cell wall, presumably, after they have cross-linked to each other. in an attempt to identify the presence of the surface water activity sensors and subsequent proteins involved in the signal cascade, we used small molecules to inhibit straw cell transformation. initial results indicated that this process could be manipulated and inhibited with naturally occurring compounds as well as synthetic compounds. for example, changes in membrane fluidity by salts and sugars disrupt the tubular transformation; antibiotics that inhibit protein synthesis interfered with the tubular transformation by producing filaments that were somewhat truncated. implication in human diseases the large quantities of straw cells and their ubiquitous nature make them a potential unifying factor across a diversity of age related diseases. the conversion of cells into straw cells may be involved in the initial onset and progression of these diseases, the causes of which are still unknown. moreover, straw cell formation may be a common physiological response in various types of human degenerative disease. another area of human health where this phenomenon may play a role is tumor development and proliferation. the hydrophilic, mobile, detachment of straw cells may be a key component of metastasis. as such, hydrophilic straw cells from cancer cells may possibly move around in extracellular fluid and find new locations to grow. there are many unanswered questions regarding the composition of these tubular cell structures found in a variety of mammalian tissues. for example, what suite of genes encodes the instructions governing the assembly of these tubular structures? what are the necessary molecules for making "unions" and "tees" in the filaments so as to form straw cell networks? is straw cell transformation a conserved mechanism that mammalian cells use in response to the stress of dehydration and perhaps other stress inducing environmental factors? what is the physiological role of straw cell formation in vivo? how much dehydration occurs inside the body either locally or systemically? because the cellular transformation is reproducible in vitro in a 96-well plate, screening chemical libraries for inhibitory compounds to filamentous transformation is feasible and may result in the ability to control straw cell development in vivo. this may have implications in mediating degenerative diseases and tumor proliferation. for example, an in vitro assay using azithromysin at ppm resulted in mammalian straw cells with both smaller straw cells and shortened filaments. one type of strategy could include selectively inhibiting protein kinases on the cell surface desensitizing the stress surveillance mechanism.  several factors bolster our hypothesis that these tubular structures are indeed special cellular structures that form when a given cell adapts to stress rather than formed from either artifacts or from spontaneous polymerization. these factors include: the pre-existence of tubular structures in all of our examined tissues; the ability to observe filamentous structures via sem, tem and light microscopy; the presence of hair-like extensions and small pores or openings on the fixed straw cells the non-production of straw cells in cell-free medium with reagents that changed osmotic potential; the prohibition of spontaneous conversion from sphere-to-straw cells by free energy; the radioisotope labeling of growth medium, showing the transformation to be a metabolically active process; the growth of straw cells into normal cells capable of dividing; the production of truncated straw cells, caused by the interference of antibiotics inhibiting protein synthesis in bacteria; the discovery that tubular walls are made of sulphated glucose polymers after purifying straw cells in gram quantity, and subjecting them to ftir and mass spectrometry analysis. we propose to call these tubular structures transformed through dehydration, "straw cells" because the filaments they produce appear to act as a conduit for the transport of water much like a drinking straw. similar to the fungal spores, the straw cells are produced by a survival mechanism to protect them from stressful conditions and then revert to a normal morphology when the environment becomes favorable. understanding the function of these straw cells and developing methods to interrupt their production is may elucidate the cause and effect of the basic pathogenesis in degenerative diseases including malignant tumor metastasis. 
this may be due to the invisibility of these cells in aqueous solution, and because sugars and salts added to the cell culture for manipulation of the osmotic conditions inhibit transformation of normal cells into tubular shaped structures. the disintegrative, mobile, disruptive and ubiquitous nature of straw cells makes this a possible physiological process that may be involved in human health, longevity, and various types of diseases such as cancer. straw cells are specialized cellular structures and not artifacts from spontaneous polymerization, which are generated in response to stress conditions, like dehydration. the tubular center of the straw cells is much smaller than the original cell; houses condensed organelles and have filamentous extensions that are covered with microscopic hair-like structures and circular openings. like various types of microbial spores, straw cells are resistant to harsh environmental conditions such as uv-c radiation. the number of straw cells in heart, lung tissues, and collapsed straw cells in urine increases with the age of the mammal. we have termed these transformed structures'straw cells' which we have associated with a variety of human tissue types, including fresh, post mortem and frozen lung, liver, skin, and heart. we have also documented the presence of straw cells in bovine brain and prostate tissues of mice. straw cells were also reproduced in vitro from human cancer cells and mouse stem cells by dehydrating cultured cells. the transformation from normal cell to straw cells takes to hr in open-air. when rehydrated, the straw cells regain their normal spherical shape and begin to divide in to days. tubular shaped mammalian cells in response to dehydration have not been previously reported. we report the transformation of normal spherical mammalian cells into tubular shaped structures in response to stress.
 tubular shaped mammalian cells in response to dehydration have not been previously reported. this may be due to the invisibility of these cells in aqueous solution, and because sugars and salts added to the cell culture for manipulation of the osmotic conditions inhibit transformation of normal cells into tubular shaped structures.  we report the transformation of normal spherical mammalian cells into tubular shaped structures in response to stress. we have termed these transformed structures'straw cells' which we have associated with a variety of human tissue types, including fresh, post mortem and frozen lung, liver, skin, and heart. we have also documented the presence of straw cells in bovine brain and prostate tissues of mice. the number of straw cells in heart, lung tissues, and collapsed straw cells in urine increases with the age of the mammal. straw cells were also reproduced in vitro from human cancer cells and mouse stem cells by dehydrating cultured cells. the tubular center of the straw cells is much smaller than the original cell; houses condensed organelles and have filamentous extensions that are covered with microscopic hair-like structures and circular openings. when rehydrated, the filaments uptake water rapidly. the straw cell walls, have a range of nm to nm and are composed of sulfated-glucose polymers and glycosylated acidic proteins. the transformation from normal cell to straw cells takes to hr in open-air. this process is characterized by an increase in metabolic activity. when rehydrated, the straw cells regain their normal spherical shape and begin to divide in to days. like various types of microbial spores, straw cells are resistant to harsh environmental conditions such as uv-c radiation.  straw cells are specialized cellular structures and not artifacts from spontaneous polymerization, which are generated in response to stress conditions, like dehydration. the disintegrative, mobile, disruptive and ubiquitous nature of straw cells makes this a possible physiological process that may be involved in human health, longevity, and various types of diseases such as cancer. 