Mechanical Model for Self-Assembly of Synaptotagmin on a Lipid Membrane

Abstract

Synaptotagmin (Syt) is a calcium-sensor that is responsible for the action-potential-controlled fusion of synaptic vesicles to pre-synaptic membranes. Recent biochemical and structural studies show that Syt can form ring-like oligomers, which occasionally convert into tubular structures on monolayer or bilayer membrane with buckled membrane inside. This suggests certain mechanical interactions between the Syt and the lipid bilayer. To explore it in detail, we developed a coarse-grained mechanical model assuming that (i) Syt self-polymerizes into an elastic chain with a spontaneous curvature; (ii) Syt attracts the membrane through binding sites located at the inner side of the Syt molecule; and (iii) membrane is a uniform sheet with constant bending rigidity and tension. Using computer simulations, we have been able to estimate the spontaneous curvature and bending stiffness of the Syt chain. The model also allowed us to understand how the Syt oligomerization depends on the strength of Syt-membrane adhesion, the bending rigidity of the membrane, and the pressure on the membrane. These experimentally testable predictions from this modelling study will provide insight into the molecular mechanism of calcium-triggered membrane fusion at the synapse.