Akimov Sergey Alexandrovich

2021 — present: IPCE RAS, leading researcher.

2021 — present: IPCE RAS, leading researcher.

2005: IPCE RAS, researcher.

2002-2005: Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences (IPCE RAS), junior researcher.

PhD in physics and mathematics majoring in biophysics.

MIPT. Master of applied mathematics and physics.

1. Lipid membranes are a barrier that controls cell metabolism. Possible violations of this barrier mechanism can lead to cell death, but, on the other hand, they have been actively studied for a long time in the perspective of biomedical applications, in particular, targeted delivery of drugs into the cell. Despite the fact that there are many experimentally proven methods of creating conductive defects in the membrane — pores through which the drug can penetrate into the cell, no physical model has been proposed that takes into account all stages of formation, growth, and the stability of such pores. Within the framework of the theory of elasticity of liquid crystals, a complete physical model of the formation of pores in membranes was built. The main value of this model is that it helped explain inconsistencies that have been observed in previous experiments conducted around the world over the past 40 years. The resulting model has not only an explanatory, but also predictive value: it can be used to describe in advance how the membrane will react to a particular impact.
   • Akimov S.A., Volynsky P.E., Galimzyanov T.R., Kuzmin P.I., Pavlov K.V., Batishchev O.V. Pore formation in lipid membrane I: Continuous reversible trajectory from intact bilayer through hydrophobic defect to transversal pore. Scientific Reports, 2017, V. 7(1), 12152.
   • Akimov S.A., Volynsky P.E., Galimzyanov T.R., Kuzmin P.I., Pavlov K.V., Batishchev O.V. Pore formation in lipid membrane II: Energy landscape under external stress. Scientific Reports, 2017, V. 7(1), 12509.
   • Akimov S.A., Aleksandrova V.V., Galimzyanov T.R., Bashkirov P.V., Batishchev O.V. The mechanism of pore formation in stearoyleoylphosphatidylcholine membranes under the action of lateral tension. Biological membranes, 2017, V. 34, pp. 270–283.
2. Currently, there is an urgent need to search, develop and introduce new antimicrobial drugs. Due to their high variability, microorganisms develop resistance to available antibiotics over time. Antimicrobial peptides are one of the promising classes of antimicrobial agents. They are able to create stable pores in the cell membranes of bacteria, which leads to the death of the latter. However, the mechanism of this process, and, as a consequence, the criteria for searching for the optimal structures of such drugs are still unclear. Within the framework of the theory of elasticity of liquid crystals, adapted to cell membranes, the mechanism of pore formation by a new generation of antimicrobial drugs, peptide antibiotics, was predicted. The complete trajectory of the process was constructed and the stoichiometry of the minimum complex of peptides necessary for the formation of a through pore in the lipid membrane of bacteria was determined.
   • S.A. Akimov, V.V. Aleksandrova, T.R. Galimzyanov, P.V. Bashkirov, O.V. Batishchev. Interaction of Amphipathic Peptides Mediated by Elastic Membrane Deformations. Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology, 2017, V. 11, No. 3, pp. 206–216.
   • Kondrashov, O. V., Galimzyanov, T. R., Jiménez-Munguía, I., Batishchev, O. V., & Akimov, S. A. Membrane-mediated interaction of amphipathic peptides can be described by a one-dimensional approach. Physical Review E, 2019, V. 99(2), 022401.
   • Pinigin K.V., Volovik M.V., Batishchev O.V., Akimov S.A. The interaction of the boundaries of ordered lipid domains and amphipathic peptides regulates the likelihood of pore formation in membranes. Biological membranes, 2020, V. 37 (5), pp. 337–349.
3. The driving forces of conjugation of monolayer liquid-ordered domains (rafts) in opposite monolayers of the membrane into bilayer structures were determined. The mechanism responsible for the bilayer configuration of ordered domains in the membrane remained unknown for a long time. Using the theory of lipid membrane elasticity, the structure of the boundary of liquid-ordered domains in lipid membranes was established and it was shown that an equilibrium configuration corresponds to a small relative shift (~ 2-3 nm) between the boundaries of ordered domains in opposite monolayers. It was shown that an increase in this shift leads to an increase in the total energy of the system, which ensures the stability of the bilayer structure of ordered domains.
   • Galimzyanov T.R., Kuzmin P.I., Pohl P., Akimov S.A. Undulations Drive Domain Registration from the Two Membrane Leaflets. Biophysical Journal, 2017, V. 112, P. 339.
   • Galimzyanov T. R., Molotkovsky R. J., Bozdaganyan M. E., Cohen F. S., Pohl P., Akimov S. A. Elastic Membrane Deformations Govern Interleaflet Coupling of Lipid-Ordered Domains. Physical Review Letters, 2015, 115(8), P. 088101.
   • Galimzyanov T.R., Molotkovsky R.J., Cohen F.S., Pohl P., Akimov S.A. Comment on “Elastic membrane deformations govern interleaflet coupling of lipid-ordered domains” Reply. Physical Review Letters, 2016, 116, P. 079802.
4. Models of interaction of lipid domains with each other and with various membrane inclusions of lipid and peptide nature were developed. Interactions are mediated by elastic deformations of the membrane that occur at the boundaries of ordered domains and near membrane inclusions. It is shown that, depending on the membrane composition, domains can attract and merge at each collision, repulse and disperse over long distances after the collision, or collide and “stick together”, then moving together without diverging or merging. All three modes were observed experimentally in symmetric lipid membranes. In addition, it was shown that, with rare exceptions, almost all membrane inclusions are distributed at the border of the ordered domain and the surrounding membrane; in this state, the total energy of the system is minimal.
   • Pinigin K.V., Kondrashov O.V., Jiménez-Munguía I., Alexandrova V.V., Batishchev O.V., Galimzyanov T.R., Akimov S.A. Elastic deformations mediate interaction of the raft boundary with membrane inclusions leading to their effective lateral sorting. Scientific Reports, 2020, V. 10, P. 4087.
   • Staneva G., Osipenko D.S., Galimzyanov T.R., Pavlov K.V., Akimov S.A. Metabolic precursor of cholesterol causes formation of chained aggregates of liquid-ordered domains. Langmuir, 2016, V. 32, P. 1591−1600.
5. A mechanism has been established for the strong non-monotonic effect of low concentrations (0.25-5%) of linearly active components on the linear tension of liquid-ordered domains (rafts). Using the GM1 ganglioside as an example, it was shown that small amounts of linearly active components in lipid membranes are distributed in the region of the border of ordered domains, causing a decrease in their boundary energy up to 10 times. In this case, a further increase in the concentration of ganglioside leads to an increase in the linear tension due to the saturation of the boundary region of the domains with this component. Thus, a method has been obtained for controlling the average size of ordered domains by low concentrations of impurities.
   • Galimzyanov, T. R., Lyushnyak, A. S., Aleksandrova, V. V., Shilova, L. A., Mikhalyov, I. I., Molotkovskaya, I. M., Akimov, S.A., Batishchev, O. V. Line Activity of Ganglioside GM1 Regulates the Raft Size Distribution in a Cholesterol-Dependent Manner // Langmuir, 2017, V. 33 (14), pp. 3517–3524.
6. The emergence of resistance of pathological microorganisms to antibiotics is an acute problem of modern medicine. Peptide antibiotics are promising antimicrobial agents, since they practically exclude the development of resistance. One of the classic peptide antibiotics is gramicidin. This hydrophobic peptide is incorporated into the membrane and, upon trans-bilayer dimerization, forms a channel that conducts water, cations, etc.Despite the long history of research on this antibiotic, there are still many open questions about the mechanisms of its functioning and the minimum concentrations sufficient for stable activity. Within the framework of the theory of elasticity of liquid crystals, a physical model was developed for the interaction of gramicidin monomers located both in the same and in different membrane monolayers. This model was used to construct a continuous trajectory of the formation of a conducting dimer from two initially isolated monomers. From the obtained profile of the interaction energy of monomers, the critical concentration was determined at which the peptide cluster is practically not destroyed by diffusion, which ensures stable integral conductivity of even a small amount of gramicidin on large-area membranes. The presence of such a regime, as well as the calculated dependences of the parameters of the conducting channels on the properties of the membrane, agree with the available experimental data. The resulting model also makes it possible to predict the dependence of the lifetime of the conduction state of the channels on the peptide concentration, as well as to predict the minimum amounts of antimicrobial peptides — channel-forming agents required for their stable activity.
   • Kondrashov O.V., Galimzyanov T.R., Pavlov K.V., Kotova E.A., Antonenko Y.N., Akimov S.A. Membrane elastic deformations modulate gramicidin A transbilayer dimerization and lateral clustering. // Biophysical Journal, 2018, V. 115, #3, P. 478–493.
7. Diffusion of a proton along biological membranes is vital for the cell energy. A physical model of lateral proton transport along the membrane surface was built and it was experimentally confirmed that the energy barrier of proton escape from the surface has only an insignificant enthalpy component, a contribution that roughly corresponds to the breaking of one hydrogen bond. The dominant entropy component probably comes from the orientation of the hydrogen bonds of water molecules near the surface, which facilitate the movement of a proton along the membrane surface.
   • Weichselbaum E., Österbauer M., Knyazev D., Batishchev O., Akimov A., Nguyen T., Zhang C., Knör G., Agmon N., Carloni P., Pohl P. Origin of proton affinity to membrane/water interfaces. Scientific Reports, 2017, V. 7, 4553.
8. Theoretical models of the membrane fusion process have been developed, from the initial stage of two locally flat parallel bilayers to the expansion of the fusion pore. Possible trajectories of the process, both leading to a complete merger and “dead-end” ones, are shown. The calculated trajectories were observed experimentally. The calculated trajectories were observed experimentally. The analysis of the influence of liquid-ordered domains on the efficiency of membrane fusion and on the choice of a particular process trajectory by the system was carried out. The dependence of the rate of fusion on the pH value of washing solutions was shown theoretically and recorded experimentally; fusion at low pH is typical for the processes of cell infection with enveloped viruses. A model was developed and the conditions for self-organization of viral fusion proteins into symmetric cooperative structures were determined.
   • Akimov S.A., Kondrashov O.V., Zimmerberg J., Batishchev O.V. Ectodomain pulling combines with fusion peptide inserting to provide cooperative fusion for influenza virus and HIV. International Journal of Molecular Sciences, 2020, 21, P. 5411
   • Akimov S.A., Molotkovsky R.J., Kuzmin P.I., Galimzyanov T.R., Batishchev O.V. Continuum models of membrane fusion: Evolution of the theory. International Journal of Molecular Sciences, 2020, 21, P. 3875.
   • Molotkovsky R.J., Alexandrova V.V., Galimzyanov T.R., Jiménez-Munguía I., Pavlov K.V., Batishchev O.V., Akimov S.A. Lateral membrane heterogeneity regulates viral-induced membrane fusion during HIV entry. International Journal of Molecular Sciences, 2018, V. 19, P. 1483.
   • Akimov S.A., Polynkin M.A., Jiménez-Munguía I., Pavlov K.V., Batishchev O.V. Phosphatidylcholine membrane fusion is pH-dependent. International Journal of Molecular Sciences, 2018, 19, P. 1358.
   • Molotkovsky R.J., Galimzyanov T.R., Jiménez-Munguía I., Pavlov K.V., Batishchev O.V., Akimov S.A. Switching between successful and dead-end intermediates in membrane fusion. International Journal of Molecular Sciences, 2017, 18, P. 2598.
9. The mechanism of signal transmission through the plasma membrane of cells has been developed when the membrane receptor binds to the ligand. The signal is the formation of a bilayer ordered domain (raft) near the receptor, which penetrates the membrane through and through. A detailed analysis of possible changes in the conformation of the receptor leading to the formation of a domain around it by the mechanism of wetting has been carried out.
   • Molotkovsky R.J., Galimzyanov T.R., Batishchev O.V., Akimov S.A. The effect of transmembrane protein shape on surrounding lipid domain formation by wetting. Biomolecules, 2019, 9, P. 729.
10. Ordered lipid domains in model membranes, as a rule, are of bilayer nature, i.e. if there is an ordered domain in one monolayer of the membrane, then in the opposite monolayer in the same place there will also be an ordered domain. It has been shown that during cis-trans phototransition of diacylglycerol, in one of the chains of which azobenzene is inserted, it is possible to induce phase separation in the membrane. In this case, ordered domains are formed, and simultaneously in both membrane monolayers. Thus, domains ~ 50 nm in diameter are already bilayer, which is an indication of the bilayer of ordered cellular domains (rafts).
• Saitov A., Akimov S.A., Galimzyanov T.R., Glasnov T., Pohl P. Ordered lipid domains assemble via concerted recruitment of constituents from both membrane leaflets. Physical Review Letters, 2020, 124, P. 108102.

Scopus Hirsch Index — 19.

Number of articles on Scopus — 79

SPIN RSCI: 116401.

ORCID: 0000-0002-7916 −6032.

ResearcherID: AAJ-2454-2020.

• Bashkirov P.V., Akimov S.A., Evseev A.I., Schmid S.L., Zimmerberg J., Frolov V.A. GTPase cycle of dynamin is coupled to membrane squeeze and release, leading to spontaneous fission. Cell, V. 135, P. 1276–1286, 2008. DOI: 10.1016/j.cell.2008.11.028.
• Shnyrova A.V., Bashkirov P.V., Akimov S.A., Pucadyil T.J., Zimmerberg J., Schmid S.L., Frolov V.A. Geometric catalysis of membrane fission driven by flexible dynamin rings. Science, V. 339, P. 1433–1436, 2013. DOI: 10.1126/science.1233920.
• Horner A., Akimov S.A., Pohl P. Long and short lipid molecules experience the same interleaflet drag in lipid bilayers. Physical Review Letters, V. 110, P. 268101, 2013. DOI: 10.1103/PhysRevLett.110.268101
• Horner A., Zocher F., Preiner J., Ollinger N., Siligan C., Akimov S.A., Pohl P. The mobility of single-file water molecules is governed by the number of H-bonds they may form with channel-lining residues. Science Advances, V. 1, P. e1400083, 2015. DOI: 10.1126/sciadv.1400083.
• Galimzyanov T.R., Molotkovsky R.J., Bozdaganyan M.E., Cohen F.S., Pohl P., Akimov S.A. Elastic membrane deformations govern interleaflet coupling of lipid-ordered domains. Physical Review Letters, V. 115, P. 088101, 2015. DOI: 10.1103/PhysRevLett.115.088101.
• Akimov S.A., Volynsky P.E., Galimzyanov T.R., Kuzmin P.I., Pavlov K.V., Batishchev O.V. Pore formation in lipid membrane I: Continuous reversible trajectory from intact bilayer through hydrophobic defect to transversal pore. Scientific Reports, V. 7, P. 12152, 2017. DOI: 10.1038/s41598-017-12127-7.
• Akimov S.A., Volynsky P.E., Galimzyanov T.R., Kuzmin P.I., Pavlov K.V., Batishchev O.V. Pore formation in lipid membrane II: Energy landscape under external stress. Scientific Reports, V. 7, P. 12509, 2017. DOI: 10.1038/s41598-017-12749-x.
• Galimzyanov T.R., Bashkirov P.V., Blank P.S., Zimmerberg J., Batishchev O.V., Akimov S.A. Monolayerwise application of linear elasticity theory well describes strongly deformed lipid membranes and the effect of solvent. Soft Matter, V. 16, P. 1179–1189, 2020. DOI: 10.1039/c9sm02079a.
• Pinigin K.V., Kondrashov O.V., Jiménez-Munguía I., Alexandrova V.V., Batishchev O.V., Galimzyanov T.R., Akimov S.A. Elastic deformations mediate interaction of the raft boundary with membrane inclusions leading to their effective lateral sorting. Scientific Reports, V. 10, P. 4087, 2020. DOI: 10.1038/s41598-020-61110-2.
• Saitov A., Akimov S.A., Galimzyanov T.R., Glasnov T., Pohl P. Ordered lipid domains assemble via concerted recruitment of constituents from both membrane leaflets. Physical Review Letters, V. 124, P. 108102, 2020. DOI: 10.1103/PhysRevLett.124.108102.

R.Yu. Molotkovsky, thesis: “Theoretical study of the initial stage of protein-induced membrane fusion”, PhD student of IPCE RAS, defended on December 25, 2013, 2011-2013.

O.V. Kondrashov, thesis: “Theoretical study of interaction of proteins and nanodomains in cell membranes, mediated by deformation of lipid bilayer”, PhD student of MIPT, defended on December 25, 2019, 2016-2019.

K.V. Pinigin, thesis: “Study of physical consequences and possible applications of corrections to the elastic energy functional of lipid membranes”, PhD student of MIPT, 2019 — present.

A.A. Mukovozov, thesis: “Theoretical study of formation of through pore in bilayer lipid membrane”, PhD student of NUST MISIS, 2015-2018.

Teaching

NUST MISIS, “Physics of liquid-crystal membranes”, 1 semester, 2010–2021.

NUST MISIS, “Non-linear physics”, 1 semester, 2012–2021.

Scientific and social activities

Editorial Board member of the “Biological Membranes” journal.