Stochastic but Fine-Tuned: Dualism in Cell Membranes' Organization as Revealed by Computer Simulations

Abstract

Model lipid bilayers exhibit atomic-scale structural/dynamic properties, which help to understand complex macroscopic phenomena observed in membranes of living cells. These are: local phase separation, clustering, mosaicity of water-lipid interface, water dynamics, ability to bind external molecules (e.g., proteins). Atomistic simulations are invaluable in exploration of such effects, which still resist easy characterization in experiments. We used molecular dynamics simulations to assess physicochemical parameters of a large set of hydrated bilayers composed of lipids with different polar heads and acyl chains. Special attention was given to molecular mechanisms determining dynamic clustering of lipids and fine-tuned interplay of interactions between membrane components [1-3]. Putative relationships between lipid composition and local/integral characteristics of the bilayers were delineated. In particular, anomalous dependence on the lipid composition was observed for mixed bilayers composed of zwitterionic/anionic lipids. Also, the effects of lipid-water environment on membrane peptides and their interactions were investigated [4]. The results permit deciphering of the factors determining microscopic structural and dynamic “portrait” of lipid bilayers and assess he role of heterogeneous and highly fluctuating membrane medium in structural organization and functioning of proteins. This makes possible rational design of lipids with modified properties (e.g., capacity of H-bonding), which could presumably affect local/integral parameters of membranes. Our preliminary data show that such lipids induce significant changes of some crucial properties of model membranes. This opens new avenues in goal-oriented design of artificial membranes with engineered properties.Acknowledgements: Authors thank Russian Science Foundation (14-14-00871), RFBR, RAS MCB Program.[1] D.V. Pyrkova et al., Soft Matter 7 (2011) 2569.[2] N.A. Krylov et al., ACS Nano 7 (2013) 9428.[3] A.O. Chugunov et al., Scientific Reports 4 (2014) 7462.[4] A.A. Polyansky et al., J. Amer. Chem. Soc. 134 (2012) 14390.