Peptide-Induced Fusion of Dynamic Membrane Nanodomains: Implications in a Viral Entry

Enveloped viruses infect host cells via protein-mediated membrane fusion. However, insights into the microscopic rearrangement induced by the viral proteins and peptides have not yet emerged. Here, we report a new methodology to extract viral fusion peptide (FP)-mediated biomembrane dynamical nanodomain fusion parameter, lambda, based on stimulated emission depletion microscopy coupled with fluorescence correlation spectroscopy. We also define another dynamical parameter membrane gradient, defined in terms of the ratio of average lipid diffusion coefficients across dynamic crossover length scales, xi. Significantly, we observe that lambda as well as these mobility gradients are larger in the stiffer liquid-ordered (L-o) phase compared to the liquid-disordered phase and are more effective at the smaller nanodomain interfaces, which are only present in the L-o phase. The results could possibly help to resolve a long-standing puzzle about the enhanced fusogenicity of FP in the L-o phase. Results obtained from the diffusion results have been correlated with the human immunodeficiency virus gp41 FP-induced membrane fusion.