Domain Stability in Biomimetic Membranes Driven by Lipid Polyunsaturation

Biological membranes contain a broad
variety of lipid species whose
individual physicochemical properties and collective interactions
ultimately determine membrane organization. A key aspect of the organization
of cellular membranes is their lateral subdivision into domains of
distinct structure and composition. The most widely studied membrane
domains are lipid rafts, which are the biological manifestations of
liquid-ordered phases that form in sterol-containing membranes. Detailed
studies of biomimetic membrane mixtures have yielded wide-ranging
insights into the physical principles behind lipid rafts; however,
these simplified models do not fully capture the diversity and complexity
of the mammalian lipidome, most notably in their exclusion of polyunsaturated
lipids. Here, we assess the role of lipid acyl chain unsaturation
as a driving force for phase separation using coarse-grained molecular
dynamics (CGMD) simulations validated by model membrane experiments.
The clear trends in our observations and good qualitative agreements
between simulations and experiments support the conclusions that highly
unsaturated lipids promote liquid–liquid domain stability by
enhancing the differences in cholesterol content and lipid chain order
between the coexisting domains. These observations reveal the important
role of noncanonical biological lipids in the physical properties
of membranes, showing that lipid polyunsaturation is a driving force
for liquid–liquid phase separation.