Atomistic Insight into the Lipid Nanodomains of Synaptic Vesicles

Membrane curvature, once regarded as a passive consequence of membrane composition and cellular architecture, has been shown to actively modulate various properties of the cellular membrane. These changes could also lead to segregation of the constituents of the membrane, generating nanodomains with precise biological properties. Proteins often linked with neurodegeneration (e.g., tau, alpha-synuclein) exhibit an unintuitive affinity for synaptic vesicles in neurons, which are reported to lack distinct, ordered nanodomains based on their composition. In this study, all-atom molecular dynamics simulations are used to study a full-scale synaptic vesicle of realistic Gaussian curvature and its effect on the membrane dynamics and lipid nanodomain organization. Compelling indicators of nanodomain formation, from the perspective of composition, surface areas per lipid, order parameter, and domain lifetime, are identified in the vesicle membrane, which are absent in a flat bilayer of the same lipid composition. Therefore, our study supports the idea that curvature may induce phase separation in an otherwise fluid, disordered membrane.