The Molecular Structure of the Liquid-Ordered Phase of Lipid Bilayers

Molecular dynamics simulations reveal substructures within the liquid-ordered phase of lipid bilayers. These substructures, identified in a 10 μs all-atom trajectory of liquid-ordered/liquid-disordered coexistence (L_o/L_d) are composed of saturated hydrocarbon chains packed with local hexagonal order and separated by interstitial regions enriched in cholesterol and unsaturated chains. Lipid hydrocarbon chain order parameters calculated from the L_o phase are in excellent agreement with ²H NMR measurements; the local hexagonal packing is also consistent with ¹H-MAS NMR spectra of the L_o phase, NMR diffusion experiments, and small-angle X-ray and neutron scattering. The balance of cholesterol-rich to local hexagonal order is proposed to control the partitioning of membrane components into the L_o regions. The latter have been frequently associated with formation of so-called rafts, platforms in the plasma membranes of cells that facilitate interaction between components of signaling pathways