Molecular Structure and Permeability at the Interface between Phase-Separated Membrane Domains

Phase-separated membrane domains,
also known as lipid rafts, are
believed to play an important role in cell function. Although most
rafts are sterol-enriched membrane regions, evidence suggests that
living cells may also contain gel-like rafts. Interactions between
gel and fluid domains have a large impact on membrane properties,
as is the case with permeability. The membrane permeability may reach
a peak at the main phase transition temperature, by far exceeding
the values recorded at the fluid phase. It has been proposed that
gel–fluid interfaces are leaky, but the effect has not yet
been demonstrated at the molecular level. Here, we performed atomistic
molecular dynamics simulations of phospholipid bilayers with coexisting
gel-like and fluid domains. We found that the thickness mismatch between
both phases, the membrane elasticity, and the lipid packing acted
together to promote the formation of a thickness minimum at the gel–fluid
interface. Free energy calculations showed that pore-mediated ionic
permeation was strongly facilitated at the constriction region, whereas
water permeation by simple diffusion was only marginally affected.
Long-lived, peristaltic undulations were recorded at the bulk fluid
phase near the main transition temperature. They gave rise to thickness
minima that, although shallower than the interface constrictions,
could also enhance permeability. Finally, we demonstrated that an
interface constriction was also formed at the boundaries of regular,
cholesterol-enriched lipid rafts. Our simulation results will hopefully
contribute to a better understanding of biological processes such
as transport, signaling, and cellular damage promoted by low temperature
and dehydration.