Lysozyme Amyloid Modulates Membrane Structure and Hydration and Impacts Its Fusogenicity

Lysozyme, which is abundantly found in cellular environments, can form cytotoxic amyloid fibrils under stressed conditions. While amyloid formation leads to the loss of enzymatic function of lysozyme, its effects could extend beyond this, as the fibrils could interact with lipid membranes and impair their fusion propensity, which is harmful to membrane functionality, like particle degradation and triggering of immune responses. To address this, we investigate the interaction between lysozyme fibrils and two model liposomes: an ordered raft-like mixed membrane composed of DOPC-sphingomyelin-cholesterol and a less-ordered non-raft-like membrane DOPC. Dynamic light scattering, fluorescence spectroscopy, and scanning electron microscopy studies reveal that lysozyme amyloids do interact with the lipid membranes and alter their ordering; THz-Fourier Transform Infrared Spectroscopy (FTIR) measurements show that membrane hydration also gets perturbed. The liposomes, in the presence of the amyloid, show significantly reduced fusion propensity; interestingly, the decrease in fusion propensity is found to be less pronounced in the mixed raft-like membrane compared to non-raft-like membranes. The mixed raft-like membranes, owing to their ordered structure, modify the hydration in a manner that fusogenicity is retained to a greater extent than in the non-raft-like liposomes.