The Effects of Domain Formation on Lipid Membrane Dynamics*

Cell membranes control life functions with unparalleled efficiency through highly regulated spatiotemporal interactions between membrane components. The rich diversity of membrane lipids plays a key role in this regulation, resulting in dynamic phase separation into distinct lipid domains that differ in their composition and biophysical properties. However, how domain formation influences membrane dynamics remains poorly understood. Here, we use neutron spectroscopy and molecular dynamics (MD) simulations to selectively study the dynamic response of the lipid matrix to the formation and growth of ordered domains. Our studies utilize binary mixtures of DMPC (14:0 PC) and DSPC (18:0 PC). Experiments show that the presence of DSPC-rich domains causes an effective slowdown in the bending fluctuations and diffusive dynamics of the otherwise fluid DMPC-rich matrix. Complementary MD simulations on analogous bilayers suggest that the measured changes in diffusive and collective matrix dynamics are mediated by interfacial DMPC lipids that experience constrained diffusional jumps and longer residence times at the domain boundaries. These findings present striking evidence of dynamic coupling between lipid domains and their surrounding lipid environment. More importantly, this interplay occurs on ns timescales of protein conformational changes – suggesting an intriguing mechanism by which domain formation regulates functional processes through synergistic modulation of membrane dynamics.