The Molecular Structure of the Liquid Ordered Phase

Molecular dynamics simulations reveal substructures within the liquid-ordered phase of lipid bilayers. These substructures, identified in a 10 $\mu $sec all-atom trajectory of liquid-ordered/liquid-disordered coexistence (L$_{\mathrm{o}}$/L$_{\mathrm{d}})$, are composed of saturated hydrocarbon chains packed with local hexagonal order, and separated by interstitial regions enriched in cholesterol and unsaturated chains. Lipid hydrocarbon chain order parameters calculated from the L$_{\mathrm{o}}$ phase are in excellent agreement with $^{\mathrm{2}}$H NMR measurements; the local hexagonal packing is also consistent with $^{\mathrm{1}}$H-MAS NMR spectra of the L$_{\mathrm{o}}$ 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$_{\mathrm{o}}$ 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.