The key to the cell: how to open the living gate of the membrane

The lipid membrane of the cell - the basis of the cell wall of any living organism - is an amazing smart “fence” through which the cell communicates with the body, feeds, breathes, protects itself from invading invaders and outsiders, lets in the necessary substances and closes itself from unwanted ones. This is a complex of security measures with selective influence. The main tool of this biochemical “communication” is pores, optional openings in the membrane. A kind of access gateway, which scientists are actively studying and describing in order to further manage it for their own - well, of course, good purposes.

What is the essence of the research and what has been done

Scientists for the first time fully described the process of the formation of pores in lipid membranes and carried out a computer simulation of their formation and evolution. They created a large-scale theoretical model that explained inconsistencies in previously obtained experimental data from other studies and resolved the accumulated contradictions.


Figure 1 is a computer model of the formation of pores in a biological membrane.

The results of the collaboration of scientists from NUST "MISiS", Institute of Physical Chemistry and Electrochemistry named after A.N. Frumkin RAS and the Institute of Bioorganic Chemistry named after academicians M.M. Shemyakin and Yu.A. Ovchinnikov of the Russian Academy of Sciences under the supervision of Oleg Batishchev was published in two parts in the journal Scientific Reports: first , second .

Lipid membranes are membranes that separate cells and their organelles from the external environment. These structures perform a number of important vital functions, in particular, they become the barrier that controls cell metabolism. Possible violations of this barrier mechanism have been actively studied for a long time in the light of drug development and therapeutic strategies, such as drug delivery, since it is the membrane that ultimately decides and determines whether a substance enters the cell. Accordingly, the algorithm of the “correct” penetration of a substance through the membrane by creating a pore is the ID card in the living cell.

Despite the fact that there are many experimentally proven methods in the world for creating pores in a membrane through which a drug can enter a cell (for example, an antibiotic to kill bacteria or an antitumor toxin to destroy cancer cells), there is still no physical model, which describes the formation, growth and stability of such pores.

As done

The authors set themselves the goal of creating a complete theoretical model that would describe all the stages of pore evolution in a lipid membrane. This task is complicated by the fact that any attempts to present the membrane as an ideal elastic shell without taking into account the peculiarities of the internal structure of the living "fence" led only to a simplified and therefore very rough description of this system. To eliminate such problems, scientists began with the fullest possible theoretical description of the membrane, and then using a series of transformations obtained expressions for pore energy, which allows describing the state of the pore depending on its geometrical parameters.

With the help of a new computer model, scientists were able to explain the inconsistencies observed in many papers devoted to this topic. This model not only explains the mechanism of the formation of pores in the membrane , it can be used to describe in advance exactly how the membrane responds to mechanical (prick, puncture) or electromagnetic effects (point field irradiation): in some cases it leads to controlled formation of pores of certain sizes and in some cases, to an irreversible rupture of the membrane and cell death. This option, of course, must be excluded in the case of therapy, and vice versa — it can be widely used to directly eliminate infected cells.

In order to finally be convinced of the validity of the theory put forward, the scientists also conducted computer simulations using molecular dynamics methods, in which the lipid membrane was recreated on the scale of individual molecules. The results of these studies coincided well with the prediction of the theoretical model and the available experimental data, and also made it possible to visually “see” how the time in the virtual membrane evolves (arises, grows and expands).



The co-author of the article, researcher at the Department of Theoretical Physics and Quantum Technologies at NITU “MISiS” Timur Galimzyanov tells:

“This work required very large labor costs from all the project participants, a large amount of computer time for calculations using molecular dynamics methods carried out by colleagues from the laboratory of biomolecular modeling of the IBCh RAS; long work on building models of observable processes; and, most importantly, an enormous array of calculations, largely analytical, carried out mainly by Sergey Akimov, an employee of the Institute of Physics and Energy, RAS, and the Department of Theoretical Physics and Quantum Technologies at NITU “MISiS”.

Why done

The authors hope that their work will become the foundation for future research on the controlled delivery of various drugs into the cell. Roughly speaking, a computer model of a complex organic system - a lipid membrane - will help to select the optimal modes of exposure to it for successful passage through the cell's “gateway”, bypassing all security measures and injecting the necessary concentrations of the necessary substances inside. In addition, the new model is likely to help describe the processes associated with the violation of the integrity of the membranes, which is observed in the course of many complex and not yet treatable neurodegenerative diseases such as Alzheimer's, Parkinson's, Pick, Chorea, Huntington and so on.


3D model of the lipid membrane

Timur Galimzyanov says:

“Never before have we conducted such detailed and consistent theoretical studies. Their result fully justified the effort: for the first time we managed to build a complete model of the pore formation process in membranes, which allows us to make not only qualitative, but also quantitative predictions . ”

Researches are continuing; in the very near future, scientists plan to publish a continuation of the story.