Regulation and preservation: dual roles of cholesterol in biological membranes

Cholesterol modulates key physicochemical properties of lipid bilayers, including phase behavior, lateral organization, acyl-chain order, and permeability to small solutes. In most phospholipid bilayers, cholesterol can be accommodated in a single liquid-ordered phase up to ~50 mol%; above this saturation limit, excess cholesterol partitions into cholesterol-rich domains and, at higher concentrations, also into cholesterol crystals, while the bilayer fraction remains saturated with cholesterol. Below saturation, cholesterol's principal role is to modulate the physical properties of the lipid bilayer in a composition- and condition-dependent manner. At and above saturation, its dominant role shifts toward buffering these properties against changes in phospholipid composition, thereby stabilizing the bilayer's physical state. This concentration-dependent duality is particularly evident in model membrane systems. In specialized biological membranes with very high cholesterol content, such as lens fiber cell membranes, the stabilizing (preservative) function may predominate. This review outlines how these two functional modes of cholesterol manifest in both model and biological membranes.