Domain-induced dynamics in phase-separating lipid membranes.

Abstract

Lipid membranes have a significant role in cells, not only defining the boundaries of cells and cell organelles but also playing an active role in cell functions, including the partitioning of proteins and the spatiotemporal regulation of signaling clusters. This is facilitated by the rich lipid diversity in cell membranes, which often results in unideal mixing and subsequent lipid phase-separation into lateral compositional heterogeneities or domains. Over the past few decades, structural measurements on such membranes have shed important light on the molecular mechanisms underlying domain formation. However, major information gaps still exist in our understanding of how domain formation affects the dynamics of lipid membranes, whether in the form of collective fluctuations or molecular motions. To address this outstanding question, we use neutron spectroscopy and molecular dynamics (MD) simulations that can selectively investigate the matrix dynamics in domain-forming membranes. Specifically, our studies are performed on binary mixtures of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and deuterated 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). Experimental results, obtained by neutron spin-echo spectroscopy and neutron backscattering spectroscopy, show that the formation and growth of rigid DSPC domains causes an effective slowdown in the bending fluctuations and diffusional dynamics of the otherwise fluid DMPC matrix. MD simulations on cognate bilayers suggest that the measured changes in the matrix dynamics are mediated by interfacial DMPC lipids that experience constrained diffusional jumps and longer residence times at the domain boundaries. Our findings present striking evidence of dynamic coupling between lipid domains and their surrounding lipid environment. More importantly, this interplay occurs on the nanosecond time scales of protein conformational changes and signaling events. Put together, the results suggest an intriguing mechanism by which domain formation can play a regulatory role in functional membrane processes.