Abstract
To date, it has been reliably shown that the lipid bilayer/water interface can be thoroughly characterized by a sophisticated so-called “dynamic molecular portrait”. The latter reflects a combination of time-dependent surface distributions of various physicochemical properties, inherent in both model lipid bilayers and natural multi-component cell membranes. One of the most important features of biomembranes is their mosaicity, which is expressed in the constant presence of lateral inhomogeneities, the sizes and lifetimes of which vary in a wide range—from 1 to 103 nm and from 0.1 ns to milliseconds. In addition to the relatively well-studied macroscopic domains (so-called “rafts”), the analysis of micro- and nanoclusters (or domains) that form an instantaneous picture of the distribution of structural, dynamic, hydrophobic, electrical, etc., properties at the membrane-water interface is attracting increasing interest. This is because such nanodomains (NDs) have been proven to be crucial for the proper membrane functioning in cells. Therefore, an understanding with atomistic details the phenomena associated with NDs is required. The present mini-review describes the recent results of experimental and in silico studies of spontaneously formed NDs in lipid membranes. The main attention is paid to the methods of ND detection, characterization of their spatiotemporal parameters, the elucidation of the molecular mechanisms of their formation. Biological role of NDs in cell membranes is briefly discussed. Understanding such effects creates the basis for rational design of new prospective drugs, therapeutic approaches, and artificial membrane materials with specified properties.
Highlights
Apart from the barrier function separating contents of cells or cellular compartments from the exterior, lipid bilayer of biological membranes plays a critical role in numerous biochemical processes in the living organisms
To date, it has been reliably shown that the lipid bilayer/water interface can be thoroughly characterized by a sophisticated so-called “dynamic molecular portrait”
The role of microscopic heterogeneities in the membranes follows from the fact that the self-organization and functioning of the most important classes of membrane protein receptors, ion channels, enzymes, etc., may critically depend on the properties of the annular lipids that form one-two nearest molecular layers (e.g., [11,14,15]). Characteristics of the latter are very different from the “free” lipid bilayer membrane. ( such curvature effects on the membrane surface are purely 3D in nature, they are conveniently represented as 2D maps—e.g., via projection on the membrane plane.) Another example is that local curvature defects on the membrane surface practically determine the binding of a number of important membrane-active peptides in these regions [16], affect the processes of membrane fusion [17], etc
Summary
Apart from the barrier function separating contents of cells or cellular compartments from the exterior, lipid bilayer of biological membranes plays a critical role in numerous biochemical processes in the living organisms. The most important are: (1) their structural characteristics, expressed in terms of the density of molecules and individual atoms, as well as describing the relief of the molecular surface of the lipid bilayer; (2) the surface distribution of their hydrophobic/hydrophilic and/or electrostatic properties; (3) dynamic parameters of the membrane components due to their lateral diffusion at different spatial scales—from integral macroscopic averages to the trajectories of individual molecules and their groups Taken together, all these types of time-dependent inhomogeneities are usually combined within the concept of “mosaic picture” of the membrane-water interface. The role of microscopic heterogeneities in the membranes follows from the fact that the self-organization and functioning of the most important classes of membrane protein receptors, ion channels, enzymes, etc., may critically depend on the properties of the annular lipids that form one-two nearest molecular layers (e.g., [11,14,15]) Often, characteristics of the latter are very different from the “free” lipid bilayer membrane. Some aspects of the problem are discussed in comprehensive recent reviews [10,11,12,13,18], but here, the author would like to express his thoughts on this problem based on the results of his own long-term research in this area
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