Fine Tuning of Microscopic Properties in Two-Component Zwitterionic-Anionic Lipid Bilayers: Determinant Role of H-Bonding

Abstract

Structure, dynamics, and functioning of hydrated lipid bilayers - model cell membranes - are governed by a thin balance of intermolecular interactions between constituents of these systems. Besides the hydrophobic effect, which determines the overall bilayer skeleton, important contribution is made by H-bonds between lipids, water, and ions. This determines crucial phenomena in cell membranes: dynamic clustering, hydration, fine tuning of microscopic physico-chemical properties, which permit fast adaptation of membranes to external agents (e.g., proteins). Characteristics of H-bonds (strength, spatial location, etc.) dramatically depend on local polarity properties of water-lipid environment. Here, we calculated free energies of H-bonded complexes between lipids and water in explicit solvents of different polarity (water, methanol, chloroform) mimicking membrane environment at different depth. The strongest H-bonds were observed in nonpolar environment, although the overall bilayer organization imposes serious limitations on the distribution of various types of H-bonds over hydrophobic/hydrophilic regions (corresponding to dielectric media with low and high permeability). This creates a delicate balance, which determines a unique H-bonding pattern for each particular lipid bilayer. This was confirmed via atomistic molecular dynamics (MD) of several hydrated lipid bilayers. Understanding of the factors regulating H-bonding propensities in such systems is indispensable for rational design of new membrane-like materials with predefined properties. One example - an artificial lipid with engineered hydroxyl group - is studied via MD simulations. It is shown that such lipids can induce significant changes of key characteristics of model membranes. This opens new avenues in goal-oriented design of artificial membranes with engineered properties. Acknowledgements: Russian Science Foundation (14-50-00131), Russian Foundation for Basic Research (16-04-00578), RAS MCB Program, Supercomputer Center “Polytechnical” (St. Petersburg Polytechnic University), Joint Supercomputer Center of RAS (Moscow).