The Dynamics of a Highly Curved Membrane Revealed by All-atom Molecular Dynamics Simulation of a Full-scale Vesicle

Abstract: In spite of the great success that all-atom molecular dynamics simulations have seen in revealing the nature of the lipid bilayer, the interplay between a membrane's curvature and dynamics remains elusive. This is largely due to the computational challenges involved in simulating a highly curved membrane, as the one found in a small vesicle. In the present work, thanks to the computing power of Anton2, we present the first all-atom molecular dynamics simulation of a full-scale, realistically composed (both heterogeneous and asymmetric) vesicle of a meaningful time scale (over 10 microseconds), which reveals unique biophysical properties of various lipid molecules (diffusion coefficients, surface areas per lipid, order parameters) and packing defects in a highly curved environment. Most interestingly, a bilayer of the same lipid composition demonstrating no phase coexistence when flat shows very strong indictors of phase coexistence when highly curved. Lipid molecules found in the curvature-induced different phases are carefully verified by their distinct composition, area per lipid, parking defects, as well as diffusion coefficient. The result of the all-atom molecular dynamics simulations is consistent with previous experimental and theoretical models and enhance the understanding of nanoscale dynamics and membrane organization of small, highly curved organelles.