Membrane Binding of Alpha-Synuclein Confers Steric Stabilization of Nanoparticle-Supported Lipid Bilayers

Abstract

The intrinsically disordered α-Synuclein (αS), upon membrane binding, forms a partially ordered complex with the first 100 residues forming a helical structure on lipid surface and the remaining 40 residues (also referred to as the C-terminal domain) retaining polymer-like, intrinsic disorder. We question the possible functional role of the partially ordered structure of αS bound to the membrane. Our previous work has shown that αS, above some critical surface coverage, sterically stabilizes silica nanoparticle-supported lipid bilayer (SSLBs), inhibiting attractive inter-membrane interactions. The disordered C-terminal domain, much like grafted polymers on surface, may predominantly contribute to steric stabilization of lipid membrane surfaces. Using small angle X-ray scattering, we have examined αS-bound SSLBs under depletion force induced by polyethylene glycol and found the critical osmotic pressure at which SSLBs aggregate to a condensed state. We find that the full-length αS sterically stabilizes SSLBs up to a critical pressure of ∼1.3 x 105 Pa, but the C-terminal domain truncated αS only does so up to ∼1.9 x 104 Pa. Under high salt conditions up to 1M NaCl, the critical pressure decreases significantly but remains higher than that required to condense SSLBs without αS. The αS-induced steric stabilization is therefore a result of both steric and electrostatic repulsion. Our data suggest that the presence of disordered C-terminal domain definitively disrupts membrane-membrane interactions and may modulate synaptic vesicle recycling.