Institute for Integrated Cell-Material SciencesVol.

72019 March

Kyoto University

contents

02

FeatureRevival after a Century!
Mechanobiology has the potential
to discover the secret of life

06

iCeMS Frontrunners
Kaoru Sugimura
Expressing the mysteries of nature
in astonishing new ways

09

The Other Half of iCeMS
Kazumi Arimoto
By using “Bayesian force inference”, forces
acting between cells were visualized. Based on
microscopic observation of the pupal abdomen offruit fly, maps of cell junction tensions (lower left)
and cell pressures (upper right) were obtained bysolving force balance equations. Turn to page 6
to read the full story.

Overseas Researchers Support Office10

iCeMS in brief

Feature

has the potential
Revival after a Century! Mechanobiology
to discover the secret of life

Bodies of living things, including mankind, consist of cells and tissues. How can a cell or tissue change its form or keep
its structure? Life is still full of unknown secrets. There is a discipline that aims to elucidate the secret of life, known as"mechanobiology." This field of science, a challenge raised a century ago, has grown remarkably in this past decade,gradually elucidating the roles that physical forces play inside the body. In this issue, iCeMS researchers working in thischallenging field introduce the fascinating points and prospects of mechanobiology.

Seeing through the lens ofmechanobiology
Molecular motor
Mitochondria
Microtubules

Why mechanics?
Mechanobiology is a field of sciencethat studies how forces produced within and between cells affect the functions of cells and tissues. The key word
is force. Mechanics take place in every
part of a living body. For example, a cell
can move by kicking its substrate by virtue of action and reaction forces. Eggs
or fertilized eggs are transported in thefallopian tube, while foreign substances
are expelled from the airway by the motion of cilia. Thus, without a mechanics
perspective, you cannot scientificallyexplain events taking place in your own
body. Someday, when the mechanicsof life are elucidated in detail, we mayunderstand the workings of the humanbody and throw light on the differences
between living and non-living things.

Kaoru Sugimura

Naotaka Nakazawa

Born in 1978 in Hyogo Prefecture. PhD,
Graduate School of Science, Kyoto University. After working as a JSPS Research Fellow
and RIKEN Postdoctoral Researcher, she
served as an iCeMS Assistant Professor. In
2017, she took up her present post.

Born in 1984 in Gunma Prefecture. PhD,
Graduate School of Industrial Scienceand Technology, Tokyo University of Science. He took up his present post in 2017
after serving as a Research Fellow at JSPS
(DC1) and at the Mechanobiology Institute, National University of Singapore.

Program-Specific Research Center
Associate Professor

Compressive Force

Stiff scaffolding

A bridge is constructed by considering forces between stones.
Likewise, the structure of a livingorganism is understood by considering the forces between cells.

Soft footholdOn firm ground, you can run fast; while on muddy
ground, you will be running slowly. This is also true
with cells. Cells can move by kicking their substrate.

1995 Beads-based traction force microscopy

Around 2000
Live imaging

Around 2010 Development of mechanicalmeasurement technology for living tissues

21stCentury

1917
D'Arcy Thompson
publishes On Growthand Form.

2

Courtesy of Dr Nobuhiro Morone(University of Cambridge)

Morphogenesis (jostling cells)

Along the microtubules of the cytoskeleton, mitochondria (cell organelles)
are carried by motor molecules.

Live imaging of awing epithelium ofa fruit fly. Numerous
cells apply forces toeach other at many
locations.

Load

Starting About a Century Ago : History of Mechanobiology
Around 1990
Optical tweezers

Mitochondria

Program-Specific Assistant Professor

1990
Around 1990
Atomic force microscope

2000
Late 1990s
Micro-nano fabrication

2010
2000s Development of mechanicalmodels of cells and tissues

Although regarded as a new field of science, the origin oftechniques at the time were inadequate for thorough re-cent imaging and micro-nano fabrication. These develop-

mechanobiology is not new, tracing back around a century ago. In 1917, the biologist D'Arcy Thompson publishedsearch, and Thompson’s questions remained unaddressed
for some time.

ments enabled researchers to quantitatively examine howmechanical forces organize the living system. Presently,

On Growth and Form. He proposed that physical or mathematical logic could explain the formation of the structuresand patterns of animals and plants and that a living organism’s form was related to mechanical forces. Nevertheless,

Around the turn of the century, many shifts in research
perspective and technology occurred simultaneously inmany fields of natural science including the developmentof mechanical measurement techniques, such as fluores-

knowledge and techniques from many fields are utilized toaccelerate research activities. After a century, Thompson’squestions have been revived, and researchers are addressing these challenges in a renewed effort.

nocha
me logybio s 1lenObservations of life from a mechanical perspective and using advanced technologies
that evolved in the 21st century have enabled researchers to understand cells andtissues in new ways. Let us briefly see the world through the lens of mechanobiology.
It may lead to discoveries beyond generally accepted ideas.

How do forces
work in a body?
Approximately 37 trillion cells make up your body. Cells
form tissues and organs, which in turn assemble into an individual body (human body). A hierarchical framework canrepresent the structure of a human body. In a cell, molecular motors generate forces, thereby deforming and moving
the cell. Under these forces, cells jostle each other, acting
on neighboring cells. By generating sensing, and reacting
to forces, cells also influence the next hierarchical tier. Researchers in mechanobiology must understand the functions and structures of molecules and cells not only from a
microscopic, but also from a multi-scale perspective.

nocha
me logy
o
i
b
s2
len

Hierarchy
in living
body

Molecule:
DNA and protein

Cell:nerve cell

Tissue:assembly of nerve cells

Organ:
brainsIndividual body:human

The fate of a cell is determined by the mechanical environment
Cells not only sense forces, but they respond to the stiffness of the tissues around them. For example, mesenchymal stem cells differentiate into bone, muscle, or vascular endothelial cells and are highly regarded
for their potential use in regenerative medicine. In 2006, it was found that substrate stiffness determines thetype of cell into which these cells differentiate. For example, if the substrate is soft, the mesenchymal stem
cell becomes a nerve cell; if hard, a bone cell; and if intermediate, a fat cell. The cell detects the substrate
stiffness as a mechanical signal. Inside the cell, it is converted into a biochemical signal and transmitted to
the nucleus. This process modulates gene expression to influence cell differentiation. In this way, the fate of acell is determined by the mechanical characteristics of its environment.
Bone cell

Mesenchymal stem cell

Nerve cell

Cell

Micropillar

Culturing cells on a substrate that has
micro-pillars makes it possible to visualize how the cells holds onto the substrate. The figure above schematicallyillustrates the behavior of the cells. The
opposing red arrows, which indicate thedirections of the motion of pillars, revealthat the cells are pinching the substrate.

3

Feature : Revival after a Century !

How do you pursue research? — Research methods and techniques

iCeMS' Approach

In the study of mechanobiology, it is necessary to look into the behaviors of cells and molecules in great detail. Various methods and techniques areused for this research, some of which are described below from the three perspectives of observation, measurement, and manipulation.

Observation

Measurement(live imaging)Live imaging enables researchers to visualize and externally observe the dynamics of living tissues and cells andthe action of gene expression. The
key is to attach a green fluorescentprotein (GFP) or a similar marker
to a living cell or protein. Doing soallows for observation of the behavior of cells or proteins in living
tissue using a fluorescent microscope or other instruments.

Live imaging enables
viewing the microtubule and cell nucleus of a neuron isolated from the brain ofa mouse.
L e f t : m i c ro t u b u l e(green); Middle: cell
nucleus (magenta);
Right: the superimposed image

Measuring methodby using a force sensor

When the micropipette tip contacts
a cell or tissue sample and a negative pressure is applied, the sample
is sucked up. Based on the sample
deformation, the sample’s absolutevalue of surface tension is measured.

(oil droplet technique)

R

Rp

∆P

∆P＝2γ（

1
Rp

-

1
R

）

The surface tension is measured
by controlling the vacuum level tomake the sucked part of the sample
a complete hemisphere.

Surfactant

Fluorescentmolecule

Oil droplet
Cell 1
Cell 2The oil droplet is coated with surfactant, fluorescent molecules, andcell adhesion molecules. Inserting
the droplet between cells enables
measurement of forces/stresses acting between cells.

column Quantitative Datawith numbers are referred to as"quantitative data."
Full use of the above-described
techniques enables obtaining

Courtesy of Dr Gianluca Grenci (Mechanobiology Institute, National University of Singapore)

4

Tissues in our body, such as muscles, bones, andnerves, possess optimal levels of “stiffness/softness”. Cells sensitively feel how stiff/soft their surrounding environments (called extracellular matrices) are, and they adapt their shape and function
accordingly. Physicists are not only good at measuring the stiffness of cells and extracellular environments, but also creating an innovative way to
calculate the order of cells and tissues. With aid
of materials that can flexibly change their stiffness
and orientation, we tightly collaborate with medical
doctors and biologists, and elucidate how dynamicchanges in the cellular environment affect the fateof cells, such as healthy cells becoming sick.

In cultured brain sliceinIn cultured brain slice

quantitative data to analyze thecomplex workings of life. Scientific understanding of phenomena in mechanobiology, and in other fields as well, requires objective and detailed numbers that
preclude subjective impressions and vague information. Researchers can construct theoretical models or discover unknown mechanisms of life by acquiring,comparing, and analyzing a vast amount of quantitative data on a daily basis.

00SecondSecond

In 3D
micro
patterned
substrate
In 3D
micro
patterned
substrate

Top: Neuronal dynamics incultured brain slice. (Magenta: cell nucleus; Green:
Migratory
cytoplasm). Neuronal midirection
Migratory
direction gration is accompanied by
the dynamic deformationof the cell nucleus.
360
Bottom: Neuronal migra360
tion in micro patterned
substrate with a confined
space (Magenta: cell nucleus; Green: cytoplasm).
This pattern is modulated
by microfabrication techniques. Scale bar = 5 µm

Naotaka Nakazawa
In the brain development, each newborn
neuron migrates from its birthplace to its
functional place through very confined spaces formed by complex neurite configurations
and extracellular matrices. Many mysteries remain
unsolved in this process, such as how mechanicalforce contribute to neuronal migration in very narrow spaces and how neurons respond to mechanicalstress by confined space during its migration. We work onthese questions focusing on the nuclear dynamics during theneuronal migration in nervous tissue.

Oil droplet

Information that can be measured, compiled, and analyzed

Images of various cell substrate surfaces
taken with a scanning electron microscope.
Using microfabricated molds and biomaterials, researchers can develop cell substrates with various structures and patterns.

inMotomu Tanaka

Cell adhesion
molecule

In tissue

Manipulation (microfabrication)
Polymer materials, such as polydimethylsiloxane and polyacrylamide,
can bond cells when they are surface-coated with a protein that serves
as a cellular scaffolding, In this process, it is possible to form scaffolding of various stiffness levels by varying the proportion of the cross-linking agent. Moreover, by combining the scaffolding with a microfabricated substrate, it becomes possible to change the cell adhesion pattern
and form a channel for the passage of cells.

When an oil droplet is inserted
between cells, the droplet is deformed due to the forces exerted
by the neighboring cells. By previously measuring the surface tension of the oil droplet in a solution,
the forces exerted by the neighboring cells can be calculated.
In solution

Bra
Bra

Specially Appointed Professor (iCeMS-CiMPhy)

Direct contact with samples(micropipette technique)

At iCeMS, some researchers work on mechanobiology. They all similarly aim to elucidate the workingsof life from a mechanics perspective. However, their focuses vary in terms of scale. The following is an
overview of the research.

Observations of how cells react to a change in the topographic orientation. Cells thatdevelop into muscles (myoblast cells) on a substrate withfine “wrinkles” adapt the shapeand the order of cytoskeletons(green) in response to changes
in the wrinkle direction.

Kaoru Sugimura
How do cells push and pulleach other to trigger precise deformations of a tissue when shaping
the body? The answer to this central
question is essential for understanding
the development of diverse forms in natureincluding our body. We have combined physics,
mathematical statistics, and live imaging to infer forces acting between cells from the observed geometry of cells. By applying the method to fruit fly wing, we discovered that mechanicalforces act as a messenger to transmit information between cells.

Tissue extension

Tension
Cell rearrangement

TensionTensionWith wing epithelia of
Drosophila (fruit flies),
tensile stress alongtheproximal-distal
direction of a tissue(the direction frominside to outside of
the body) determines
the direction of cell
rearrangement. At thepink locations in the
figure, cell junctions
are remodeled andcells rearrange without being tore up under tensile stress.

58Interview

The process by which cells proliferate and differentiate, growing from a fertilized egg into an organism body, is called“development”. In the process, cells push and shove within the growing body, exerting force against one another.
With the clarification of the chemical signaling pathways that control development, researchers turn to the questionof how mechanical forces affect the shapes of organisms. Associate Professor Kaoru Sugimura’s work is devoted tounraveling the mysteries of living organisms, a quest that centers on the “mechanical force in living things”, as she
gleans from a wide variety of fields, including imaging technology, soft matter physics, and mathematical statistics.

Expressing the mysteries of nature
in astonishing new ways
Kaoru Sugimura

Program-Specific Research Center Associate Professor

Career summary on page 2

6“This is live-cell imaging of a fruit
fly wing,” says Sugimura, as she turns
the laptop on her desk to face us. The
screen shows a fly wing taking form.
Countless shining cells slowly migratefrom the tip toward the body of thewing. The fantastic sight recalls theMilky Way twinkling in the night sky.
“Fruit fly wings help us understand thefundamental logic of development. I’ve
been using fruit flies for experiments
and mathematical modeling since mystudent days. Collecting quantitative
data is indispensable for my research,and flies are an outstanding tool for
quantitative study of genetics and development. They are also easy to analyze.
And so…. ” Her words speed up as her
voice rises. The flies that gather aroundkitchen garbage might just annoy mostpeople, but for Sugimura, they are special creatures that support her research.
The way she talks about them gives us
a sense that she sees them as more thanexperimental organisms - that she may
actually feel affection for them, allowing
some genuine feeling to filter throughImage of a fruit fly wing, in which E-cadherin
is labeled with GFP
A wing in the pupal stage. Observation ofcell movement is enabled by fluorescently
labeled E-cadherin, cell adhesion molecules.
A pulling force acts from the body (left), andin response, cell groups flow from right to left.

her scientific work. Where might thishave come from?

Life direction changed
by science experiments
As a little girl, Sugimura was a bookworm. She would lose herself in endlessbooks about anything that caught her
fancy, from space and science to dinosaurs and stories. She had no interest in
the toys and dolls that held the attentionof girls around her, but she would beg herparents to buy her books. Spreading thewings of her imagination, she voyaged
far through reading. “I wanted to growup to be someone who expressed what
the world is like. Sometimes I thought
about being a writer or a film director,
although, even as a child, I suspected mytalents did not lie in those directions. ”
The turning point in her interest
was a science class in middle school.
Sugimura was totally absorbed even bysimple experiments, such as observing
a rolling ball or a swinging pendulum.
“I was in a group of four girls doing
experiments, and the other three weren’tinterested at all. But I got really excited.
I thought to myself, this is something I
could keep doing. ”
At first, it was physics and chemistrythat held her interest. Compared tothe physical sciences, where problems
are precisely solved with mathematicalformulas, biology seemed ambiguous
and vague and therefore completely

uninteresting. “Then during the summer
break in my first year of high school, I
happened to read a book about the beginnings of molecular biology, and thescales fell from my eyes. The workingsof living organisms could be explained
in logical terms! My inclination shifted
180 degrees. I suddenly knew I wanted
to study biology from the perspective ofphysics, and it filled me with excitement. ”

An innovative method ofquantitative research
About ten years later, as a researcher at
RIKEN, she entered the emerging fieldof mechanobiology, a fusion of biology
and physics. “In graduate school, I used
live-cell imaging and molecular genetics to analyze the mechanisms of nerve
cell dendrites. Just before finishing my
PhD, I attempted a mathematical modelof dendrite formation based on my own
experimental observations. For this, I
had to incorporate information from avariety of scientific fields. Later, throughinteractions with many scientists, including my current collaborator, I realized thatmechanical force plays an important rolein the process of development. ” At thattime, very little progress had been made in

An inverse problem between cell shape and force is solved by using Bayesian statistics. It infers
relative values of cellular forces from the observed geometry of cells.
a. Diagram of the force acting on the vertex of a cell. T denotes tension at the cell adhesion
surface; P denotes cell pressure.
b. Formulation of the inverse problem derived using Bayesian statistics. The posterior
distribution function, obtained by multiplying the likelihood function and prior distribution, gives
the estimated value of forces.
c. Example of application of Bayesian force inference. Tension at cell junctions and cellpressures are shown (Image was take in fruit fly wing epithelium at 23 hours after pupation).

7

understanding this aspect of development,
as the mechanics of biological tissue werestill largely unknown. She plunged wholeheartedly into elucidating them.
Sugimura collaborated with Shuji
Ishihara, an associate professor at the
University of Tokyo, to measure physical forces in cells. They worked not byapplying external force, but by visuallyquantifying the force received by individual cells. They established “Bayesianforce inference” to estimate relativevalues of tension in surfaces contacted
by other cells and pressures on the cells.
“Simply put, the technique estimates theforces acting on cells by analyzing cell
shapes in images. When force is applied
to something, its shape changes. We
set out to measure that force based on

Playing soccer on a futsal field with fellows
from her graduate school days. Having
played soccer since the first year ofelementary school, she is relaxed. Even whenbusy, she manages to play once every twomonths, working up a sweat and renewing
her energy for research. “My favorite positionis central midfielder. I have a wide field ofview, and I can think through each play. Just
like scientific research, soccer is something I
can’t do without. Soccer is life!”

8

information from the shape, reversing
the cause and effect relationship. Withother methods, like using optical tweezers that apply external forces to cells,
detailed information is obtained, though
for relatively far fewer cells. With our
method, although an estimate, the visual
data measures some 20,000 cells at one
time. ” Sugimura and her colleague
devised this method by combining amathematical statistics approach tophysics and biology. This resulted in
an innovative method of quantitative
research and an original way to “express”
the mechanisms of life.

The mysteries of life arestill quite profoundThe results of her research at RIKEN were recognized, and in April 2011,
Sugimura became a member of iCeMS.
Ever since that first aspiration to be ascientist in middle school, she has had
an inquisitive mind. “I want to uniquely
express the mysteries of nature throughmy work. This idea has always sustained
my work. Expression involves someindividuality, and I’m just not interested
in doing the same things as others. But
I’m not like a chemist who starts fromscratch and creates a new material. I
want to take what’s already in the natural
world and express it in a way that anybody can understand. ”
The mysteries of living organisms
are still quite profound. For example,

The Other Halfof iCeMS
ORSO: Overseas Researchers
Support Office

Kazumi Arimoto

At iCeMS, English is the official language, and about 20 % of the researchers come fromabroad. However, once these members take one step out of the building, they enter anotherland. People coming to Japan for the first time often encounter cultural differences andlanguage barriers. Even given cutting-edge research facilities, they cannot concentrate on
research without first having a stable living environment. One of iCeMS’ major tasks is tomaintain an environment where international researchers can feel relaxed and can concentrate.
To this end, the ORSO is advancing efforts that are gradually spreading within Kyoto University.
Kazumi Arimoto, who has worked for 7 years at iCeMS, talked to us about her job

ORSO supports in…

Commemorative photo at the “Portraits ofThought” exhibition at the Kyoto University
Museum. One of the drawings by Michael
Whittle in this exhibition is based on a
growth model for human neurons createdby Sugimura.

the DNA contained in the nucleus ofeach human cell has a string-like shape,
and when uncoiled, it is about two
meters long. That is, packed inside a
nucleus just ten micrometers in diameter
is DNA about as long as a person is tall.
Furthermore, rather than haphazardly
crammed into the nucleus in the way wemight stuff a closet, each type of cell, likemuscle cells or nerve cells, has a characteristic arrangement. “Doesn’t that makeyou wonder what it’s all about? We can’t
elucidate even such basic mechanismsof life. If we bring together knowledge
and ideas from, not only biology andphysics, but various other fields as well,and if we investigate thoroughly, thenhopefully we will understand what makeliving matter unique. I want to express
the mechanisms of life from an original
viewpoint that will astonish everyone. ”

Obtaining a status of residence

Employment procedure· Serve as a proxy applicant to receive a
Certificate of Eligibility needed for visa
acquisition· Help with the renewal orchanges of residency status· Confirm the necessary documents
when overseas workers come to theuniversity· Support for opening a bank account· Help with resident registration

To work and live in Japan, overseas workers must obtain astatus of residence in advance of their coming to Japan.
Support for obtaining this is the most important part of the job.

General matters for living in Japan· Introduce hospitals who provide service in English· Provide information on childcare, schools,
and procedures· Support for obtaining mobile phones and credit cards· Provide information about Japanese language classes· Explain administrative procedures related to childbirth

Searching for housing· Introduce university
accommodation facilities· Provide information about realestate agents who provide service
in different languages

In addition to the above, the ORSO responds to general requests
about living in Japan and may accompany researchers to
appointments, depending on the circumstances.

Provide residential information helpful forfinding accommodation.

The range of support is infinite
Arimoto•For researchers coming toJapan, the first necessity is to obtainthe status of residence. We coordinate witheach department to examine and support
the necessary preparations. In addition tosuch administrative procedures, it is also
important that we respond to researchers’
requests for consultation. Since theconsultation can cover many aspects oflife in Japan, the broad scope of this work
cannot be easily summarized. In addition,
we often receive unexpected consultation
requests. For example, a researcher with
an elementary school-aged child once

asked, "I’d like you to tell me how to do
the threadworm inspection." In his homecountry, there was no "threadworm
inspection". At that time, I tried using animage of the procedure in English, andI remember struggling to pick the rightwords to explain. In this kind of situation,
I first try to understand the matter well inJapanese myself and think about the bestEnglish words to explain with.

Responding with sincere feelings
Arimoto•Most people who comehere to consult feel uneasy, so I
take an affirmative approach, saying “Don’t
hesitate to ask for my help!" Sometimes

we may get requests that we cannot solve
directly, such as dealing with inadequate
administrative procedures. Saying, "I do not
know," will not solve such problems. We
empathize with the request and try ourbest to affirm where the problem is andwhat should be done.
In any job, I think trust and sincerity areimportant for the relationships between
people. If one party does not trust theother, then the message will not be
communicated effectively. Whether ayoung researcher or a researcher alreadyin an established position, my approach
doesn’t change. I try to respond to
everyone in the same way.

9

iCeMS in brief
Research Highlights
Creating guidelines for nanomaterial development using'unsupervised machine learning'
Daniel Packwood and colleagues made use of mathematical science,
theoretical chemistry, and materials science and succeeded in creating
guidelines for machine learning, leading to protocols for assembling
molecules on a desired substrate.
This ‘machine learning’ ascertains the relationship between
chemical features of molecules and their assembly process, graphicallysummarizing the results. Analysis of these figures leads to these machinelearning guidelines. Through this, it becomes possible to predict, forexample, which molecule to employ for a linear supramolecular structureused as electrical wiring.
There are two types of machine learning, "supervised" and "unsupervised".
The guidelines developed by this research can determine data group trends
without knowing the correct and incorrect data solutions beforehand, ameaningful predictive application of "unsuper-vised machine learning".
This result contributes to the development of microdevice parts andwill likely accelerate the development of nanoelectronics. In the future, it
may also contribute to robot and soft display development, as well as therealization of ultra-low power consumption devices.

Capturing the surprising flexibility of crystal surfaces

Molecules interact and align with each other in self-assembly.
Illustration by Izumi Mindy Takamiya

Daniel M Packwood, Taro Hitosugi (2018). Materials informatics for self-assembly offunctionalized organic precursors on metal surfaces. Nature Communications 9, 2469

Mechano-sensing and resistance during developmentof the fruitfly wing

TissueF-actin untwisted

cofilin
AIP1

F-actin
twistedIn response to tissue tension, cells change their position along the direction of tissue stress.
AIP1 and cofilin maintain the structural stability of remodeling junctions to promote directional cell rearrangement.

Keisuke Ikawa, Kaoru Sugimura (2018). AIP1 and cofilin ensure a resistance to tissue tension
and promote directional cell rearrangement. Nature Communications 9, 3295

10

Kaoru Sugimura and Keisuke Ikawa have discovered new mechanismsof force sensing and force resistance during tissue development.
The global patterns of forces in a tissue (i.e., tissue stress such as
tissue tension) control many aspects of development including cellproliferation, rearrangement, and polarity. However, the mechanism
by which cells respond to and resist tissue stress during development
remains unclear.
Sugimura’s research group found that actin disassemblers, actin
interacting protein 1 (AIP1) and cofilin, play a key role in sensing andresisting tissue tension to support directional cell rearrangement in
the fruitfly wing. Tissue tension is converted into structural changes
in the tiny actin filament, which are recognized by AIP1 and cofilin,
leading to accumulation of AIP1 on the remodeling junction. AIP1 andcofilin promote actin turnover and strengthen the structural integrityof the remodeling junction. Future studies should explore whether
the molecular mechanisms identified in the present study potentiallyfunction in other developmental contexts, such as cell proliferationand cell death.

Susumu Kitagawa’s group directly observes the crystal surface
with an atomic force microscope. With this method, for the first timethey observed the flexible and dynamic changes that occur on thesurfaces of 'porous coordination polymer (PCP)' crystals.
When the porous crystal is exposed to certain molecules,
its surface deforms from a square lattice structure to rhombic.
Although the existence of porous crystals that flexibly change thestructure when the concentration of molecules becomes equal to or
greater than a certain value was known, how the surface behaved
during this process remained a mystery.
This research found that the deformation of the surface ofthe porous crystal occurs at a lower concentration than for the
deformation of the whole crystal. This means that the crystal
surface has a more sensitive response than inside the crystal.
The application of this phenomenon could lead to a wide range of
nanotechnology, such as high-sensitivity sensors that detect trace
amounts of substances and separation membranes that selectsubstances at the nano level.

Materials that open in the heat of the moment
Susumu Kitagawa’s group has developed a new porous material
for sieving or storing different kinds of gas molecules.
They designed a porous coordination polymer that was formedof copper atoms linked by butterfly-shaped molecular “gates”. This
enables controling the pores’ opening and closing according totemperature, allowing adjustment of the flow rate of gas molecules
passing through the pores and the selection of gas types. This
makes it possible to efficiently separate and store gases.
The research group succeeded in separating molecules withsimilar properties such as oxygen and argon, as well as ethylene andethane by this method. Likewise, by controlling the release of thegas, the group also succeeded to slowly discharge the stored gas.
This research result can lead to further development of materials
for gas separation and storage, with applications such as theseparation of greenhouse gases and the storage of methane. It also
has applications for a wide range of industries, such as material forthe controlled release of ethylene gas, an important plant hormone
for ripening fruits and vegetables.

The team observed the fluctuations of the flexible PCP surface.
Illustration by Izumi Mindy Takamiya

Nobuhiko Hosono, Aya Terashima, Shinpei Kusaka, Ryotaro Matsuda, Susumu Kitagawa (2019).
Highly responsive nature of porous coordination polymer surfaces imaged by in situ atomic force
microscopy. Nature Chemistry 11(2), 109–116

Butterfly-shaped
ligands were thekey to designing amaterial that can selectively absorb andstore different gas
molecules.
Illustration by Izumi
Mindy Takamiya

Cheng Gu, Nobuhiko Hosono, Jia-Jia Zheng, Yohei Sato, Shinpei Kusaka, Shigeyoshi Sakaki,
Susumu Kitagawa (2019). Design and control of gas diffusion process in a nanoporous soft
crystal. Science 363(6425), 387–391

11

iCeMS in brief

What’s new?
iCeMS launches “Smolab” with CNRS, France

iCeMS Caravan visits high school in Okinawa

iCeMS established a joint laboratory"Small Molecule Lab (LIA-Smolab)"with the French National Center for
Scientific Research (CNRS) andothers. This collaboration aims topromote the development and application of "porous coordination polymer (PCP)" materials, which are filledwith countless small holes that cantake in gases. The October 9, 2018 signing ceremony was attended by Director Kitagawa and others. As PCP study further develops, the exchange
between Kyoto University and French research institutions will also deepen.

iCeMS researchers held an "iCeMS
caravan" on February 16, 2019 todeliver their original active-learning program to Kyuyo High Schoolon Okinawa Island. High school
students organized into groups todiscuss the caravan lectures andgave presentations at the end of the
program. The event was transmitted
live to another room, where other participants, including families and teachers experienced the same process as the students in the main room. The
program participants totaled more than 120.

AwardsActivities◦Ryoichiro Kageyama receives the Naito Foundation Merit Award(Nov 4, 2018)◦Susumu Kitagawa Selected as the 2018 Highly Cited Researcher(Nov 28)◦Koichiro Tanaka receives the Nishina Memorial Prize(Dec 6)◦Aiko Fukazawa receives the Lectureship Award MBLA 2018(Feb 1, 2019)◦Hiroshi Kageyama receives the Inoue Prize for Science(Feb 4)◦French Maison de la Chimie awards Susumu Kitagawa the Grand Prix(Feb 13)◦iCeMS Science Festival 2018 held inviting High school students(Nov 9, 2018)◦KyotoU, UCLA hold joint symposium in California(Nov 15–16)◦iCeMS joins Instagram(Dec 21)◦iCeMS Participates in the WPI Science Symposium
and Kagaku-Zammai in Aichi(Dec 26–27)◦iCeMS participates in the AAAS meeting in Washington DC(Feb 14–17, 2019)

iCeMS Fund - Help us grow
At iCeMS, researchers from Japan and abroad devote themselves to research both day andnight. Research results may sometime lead to applications, such as saving the lives of those suffering from incurable diseases or improving the global environment 100 years in the future. On theother hand, pure science we do may not be readily understood by people in the early stage. No one
can predict the landscape we will be standing in after our challenges, however, we believe that our
research will steadily advance science.
In order for iCeMS researchers to continue moving forward, it is necessary to establish a stable
fiscal foundation. We appreciate your understanding of the activities and spirit of iCeMS, and we
thank you for your continued support through the iCeMS Fund.
Contact details
Kyoto University Institute for Integrated Cell-Material Sciences
Research Administration Office
Phone: +81-(0)75-753-9749 | E-mail: innovpe@mail2.adm.kyoto-u.ac.jp
Website: u.kyoto-u.jp/kuifiCeMS
Our World, Your Future
Vol.7
2019 March

Editorial note
We featured "Mechanobiology" in this issue. We spenttime editing for the understanding of those not specialized in
the field, but this was a super complicated theme (as we expected!) and we racked our brains so much. However, what
is nice about iCeMS researchers is they always actively participate in the production of this newsletter series, andthanks to them, we have been able to deliver this completed
issue to you.
In this issue "The Other Half of iCeMS" newly started. At
iCeMS, not only researchers, but other staff members arealso working to create the best research environment in theworld. What do they do? What kind of people are they? We
will deliver stories of the other very important half of our institute. Please let us know your thoughts.

Production Institute for Integrated Cell-Material Sciences at Kyoto University
Research Administration Office Public Engagement Unit
Mari Toyama, Izumi Mindy Takamiya, Takayuki Homma
Yoshida Ushinomiya-cho, Sakyo-ku, Kyoto 606-8501, Japan | Phone: +81-(0)75-753-9753
E-mail: info@icems.kyoto-u.ac.jp | Website: www.icems.kyoto-u.ac.jp
Facebook:@Kyoto.Univ.iCeMS | Twitter:@iCeMS_KU | Instagram:@iCeMS_KU
Production/cooperation: Kyoto Tsushinsha Press, Design: Nakasone Design

Mari Toyama