# Evolution of prebiotic membrane

Abstract
I propose in this letter a new way to conceive the formation of a liposome with pores. It is a physical process that is the logical consequence of the formation of a liposome in a pocket of prebiotic petroleum as described in the article "prebiotic petroleum". The pores appear during liposome formation and the following molecular evolution serves to strengthen and make more and more functional overall.
Indeed the lipid layers, from the prebiotic soup, consist of heterogeneous phospholipids or fatty acids which be grouped, by mechanical cohesion, into sets of aliphatic chain of approximately identical lengths. This grouping is growing with enormous surface forces that occur during this formation process.
When two groups with short aliphatic chains are facing each other, the repulsion of their electric dipole forces them to adopt a minimum energy configuration, pipe-shaped membrane-spanning, aliphatic chains penetrating the hydrophobic region and the hydrophilic heads by contacting with water that may then flow between the inside and outside of the liposome.
To the breakdown in strength of the lipid layers due to surface forces and electrical repulsion of the dipoles must be added the osmotic pressure difference on either side of the membrane that forces water to pass through. This pressure difference is due to the fact that the main phase is composed of water content of the vesicles having aborted which may be different from that of the liposomes formed.
Note on 14.03.2015: This article is part of the summary of my work until 2014, published in Origins of Life and Evolution of Biospheres, March 2015.
Reference: Prebiotic Petroleum; Mekki-Berrada Ali, Origins of Life and Evolution of Biospheres, 2015, DOI 10.1007/s11084-015-9416-7.

## Introduction

Dear Iroshi Murakami,
I have read your 3 articles. Your work interests me a lot because he joined thinking that I started my analysis of the mechanical cohesion of the liposome. You can see this analysis in the poster "prebiotic chirality".
This thinking started from a problem posed me the theory of chemo-osmosis Peter D. Mitchell (1961). In fact, this theory deals with the electrochemical potential that in classical physics assumes an electro-magnetic fields acting at a distance which establishes that potential. But in liquids there is no vacuum and all local electromagnetic field is shielded by neighboring molecules before reaching the remote molecules. My study of communication through the membrane that I published in prebiotic chemo-osmosis was blocked while I attributed to the electrochemical potential driving force of molecular evolution [Part 2 of the poster "prebiotic petroleum"].
With the properties of the mechanical cohesion I thought then that a high hydrostatic pressure rigidifies the membrane and allow communication through the membrane by the process of action/reaction as in solids, and the charges accumulated on the outer face by this process would cause the ionization of internal molecules that neutralize. In fact, the electric potential is increasing.
The idea behind the high hydrostatic pressure is assumed to accelerate a process that would penetrate the amino acids in the membrane to finally establish exchange channels. Why are amino acids? Because exchange channels are protein and that the amino acids are zwitterions as the hydrophilic heads to which they can cling and come into the membrane.
This assumption penetration of amino acids in the membrane is actually built on a preconceived idea which seems logical. This logic is as follows: For the exchange through the membrane channels in molecular evolution, we must increase the permeability of the amino acids. The a priori is the prior existence of a perfect membrane as it exists in the living but without the channels. All experiments were made ​​in this logic and my thoughts until the oral delivery of professor A. Pohorille on 13/7/14 was based on this assumption.

## Evolution scenario of prebiotic membrane

With this seminar, having seen all attempts to form liposomes or for filling of pharmaceutical molecules, a new way appeared to me to perceive prebiotic permeability of liposomes. The idea would be to start with a fully permeable liposome (or with many pores) that would evolve into a liposome with a limited number of protein channels as current liposomes. I call this liposome, prebiotic liposome.

### Formation of prebiotic liposome (with pores):

The process to form the liposome is described in my poster "prebiotic petroleum" and two posters who work on the encapsulation of pharmaceuticals (D.Baigl, M. Morita ). This process is described schematically and does not address in detail the relationship of forces.
* In the aqueous vesicle of the oil phase the forces in the future inner leaflet are those of V. der Waals uniting aliphatic tails and those ionic, which bring closer zwitterionic hydrophilic heads (mechanical cohesion).
* In the main oil/water interface future outer leaflet, the forces are the same as before.
* When the aqueous vesicle bring closer to the main interface, two types of forces come into play:
   * The surface forces which involve the resistance to deformation of all the constituents of the two interfaces. We know that physics is enormous.
   * Locally electric potential difference due to the formation of two layers. These potentials are still present because the external environment is changing by definition.
* For a bilayer is formed it must overcomes surface forces and it cancels the electric potentials.
   * To overcome the surface forces, it is enough that the resulting cohesive forces of the outer leaflet be superior to them.
   * To cancel the electric potential there must have movement of ions across the bilayer, with their train of H2O hydration. This is only possible if the two sheets were heterogeneous constitution. This is the case of prebiotic soup. In the case of pharmaceutical experiences it would be difficult to obtain liposomes if pure phospholipid are used.
       Pore ​​formation is much easier when leaflets contain phospholipids short aliphatic tail. Mechanical cohesion between phospholipids causes that they congregate in areas tails substantially the same size. Areas with the shorter tails of the two sheets facing each other are subjected to their dipoles their dipoles repulsion and form tubes which aliphatic tails penetrate perpendicularly in areas that constitute the long tails bilayer.

### Evolution of prebiotic membrane (or bilayer):

* Assets: With this hypothesis of the formation process liposomes equipped with communicating pores we made a giant step forward, at least in theory. 4 points are acquired now:
   * The number of prebiotic pores relative to the volume of the liposome is determined by the surface forces in a limited narrow range. Vesicles with too small aliphatic (ie more pores on arrival) abort. Vesicles with too long aliphatic tails can not cancel the electrical potential, can not hang the outer leaflet and remain in the oil phase. This stage of evolution will be very fast.
   * Now the electrical potentials can be cancelled on a regular basis by responding to changes in the external environment, and thus play a driving role in molecular evolution.
   * Segregation Na/K can now be established without the need to know why.
   * Phosphate can now enter and be sequestered in the emerging metabolism.
These 3 points were a problem in the "prebiotic chemo-osmosis" article and the initialization of metabolism "prebiotic chirality".
* Consolidations to be made by molecular evolution:
Despite this theoretical giant step while not yet acquired and liposome can collapse because very fragile and nascent metabolism can leak through the pores. 4 consolidations must be made by molecular evolution and in some cases rapidly.
   * The number of pores may be too high relative to the volume and weaken the liposome.
   * The number of relatively not long aliphatic tails remaining in the membrane may destabilizes it by the repulsion of their head dipoles.
   * The pore characteristics are varied being issued from the prebiotic soup, and do not correspond to a consistent functioning of exchanges. For example, it may be that there is too much anionic pores (phosphate) which would prevent the entry of phosphate, too short aliphatic tails to cling to the membrane that disrupts and weakens the pore membrane.
   * Leak of molecules of the nascent metabolism would slow or stop completely the molecular evolution.
We will see that these consolidations will be via amino acids like the mechanical cohesion that I advanced in "prebiotic chirality".
   * The imbalance caused by phospholipids with no long enough aliphatic tails is a constraint for the mechanical cohesion. We saw in "prebiotic chirality" that is L-Ser plays the major role in the mechanical cohesion and may be assisted by other L-amino acids when the hydrophilic head is missing or incomplete. This constraint to mechanical cohesion can accumulate too amino acid at the inner surface which would constraint to their decarboxylation for maintaining the mechanical cohesion while eliminating the accumulation of negative charges. The evolution of nascent metabolism is enhanced because pass at a later stage of initialization what the interconversion of amino acids and oxo acids.
   * If amino acids and hydroxy acids are excluded from molecules that line the pores, these diverse and not joined together rather would not promote order. Amino acids and hydroxy acids provide solidarity among themselves through hydrogen bonds they can establish between them. In addition they may form (without being connected to each other by peptide bonds) alpha helices that strengthen the membrane with aliphatic radicals and inside the pore they expose ionised or polarized radicals which filter in many different ways, finely and variously, various ionized or polarized molecules. Alpha helices and the membrane are mutually reinforcing.
   * Molecules leak of the nascent metabolism can not be a constraint, only a selection. These are the metabolisms that store as quickly as efficiently their small molecules that will continue to evolve. On the other hand interaction between metabolism and pores is a constraint for the first. Metabolism needs effective pores to interact with the external environment.
   * Fragility caused by an excessive number of pores is reduced by the mechanical cohesion evolution. However, pore consolidation by amino acids provides an opportunity for the development of the prebiotic membrane to membrane proteins energy systems by chelating transition metal necessary to these systems such as cytochrome.

## Interpretation of the molecular evolution of the membrane.

* This means that before as we did not see changes in the membrane but changing channels. And A. Pohorille made ​​a step further by proposing the co-evolution of the membrane and metabolism. But experience has shown that clearly show the evolution of channels and metabolism, but there is still no changes in the membrane as a whole, as I said above.
* This is more physical than chemical evolution:
   * Physics: dipoles, V. der Waals forces, circulation, cohesion ...
   * Chemistry: 4 esterifications. fatty acids, phosphate, glycerol and serine in a first time and then decarboxylation of serine in a second time.
* Molecular evolution of the membrane becomes an actually co-evolution of metabolism and the membrane.
* In this hypothesis of prebiotic membrane primacy is given to amino acids and peptides.

## Study of condensed media.

If I wrote you in detail my thoughts on the molecular evolution of prebiotic membrane is to show you how complex the study of condensed media. Certainly it is a way to communicate my discoveries, but I'm trying to show you that imagination and reflection work becomes mandatory when addressing such a complexety. And this work may not be possible if it is based on simple concepts confirmed by experimentation as those developed by thermodynamics and quantum mechanics. This is why your work and that of condensed media in general are important. Because they allow us to see the behavior of an individual entity (atom, molecule) in a very simple situation that allows experimentation. I say glimpse and even guess as the sample size is very important.
* Thus in the first article of4-2011 I noticed an interesting idea. It is not that the myoglobin is in the center of the micelle, but in contact with the hydrophilic heads. This shows the importance of membrane / protein relationship in research on the origins of life. As against the conformation of this protein is distorted. This is due to the size of the micelle. Statistics were made on molecules of E.Coli and show that it is a hundred thousand times larger than the micelles that you are studying.
    The study of the organization in a bacterium is compared with the management of a country of tens of millions of people. The experiment allows only take a sample, a college class of thirty students; the rules of social organization are, but those of the management of an entire country are not there. Maybe if we had all the molecules of bacteria and their properties, one day we can with powerful computers, to apply the same business rules.
* In the second article of11-2011, teraHz technique used to study vibrations, movements, hydration and protein folding in still the reverse micelles of nanometric size. All these processes affect the enzyme activity. An important question that I asked on the enzymatic activity of proteins in the cell and not in aqueous solution: why hydrolysis/esterification reaction, the most used by the cell is always directional (one way), while that the thermodynamic reaction (outside the cell) is reversible? It is as if it did not exist in the cell and also it should not exist because there would be the enzymatic network that thwart its controls in a parallel network. It is as if the reactants and the products were not in contact with water. But then how they will spend an enzyme to another? The experiments with reverse micelles and the technology teraHz could certainly give an overview.
* The third article of11.2013 discusses the organization of water molecules in the micelle, supercooled water, under the influence of the hydrophilic heads. These experiments are very important for the research on the origin of life. These results mean that the micelle or liposome, with their hydrophilic heads create a top organization. Conceptual point of view this is huge because if we add the organization of the bilayer and its evolution as I presented above, the problem of initialization of the organization is almost solved, and thanks to 4 esterifications of three small molecules: glycerol phosphate and serine.
I hope, dear Iroshi that you will continue your research in this area, as they look very promising for research on the origins of life. As I mentioned at the beginning of this note, I wish for myself to introduce in these experiments high hydrostatic pressures as they are practised in green chemistry, at few kilobars.
Thank you again you are interested in my work.