Unified Mechanisms of Membrane Curvature Generation by Diverse Peptides and Proteins

A diverse range of biologically critical phenomena involve membrane remodeling and/or the induction of membrane curvature changes by peptides or proteins. These events require a complex interplay between biophysical properties of both lipids and proteins. In this dissertation, we examine several prototypical systems important to human health and disease: the action of antimicrobial peptides on bacterial membranes, of cell-penetrating peptides in drug delivery, of viral proteins in the entry and egress of enveloped viruses, of gamete proteins in fertilization, and of dynamin-related GTPases in mitochondrial fusion and fission. Examples of each of these processes will be engaged in detail by a chapter of the dissertation. In all of these cases, a peptide or protein precipitates topological changes that allow communication across a deformable membrane dividing two spaces, such as membrane pore formation, membrane blebbing, or membrane budding and scission. While the distinct deformations and changes to membrane morphology in these processes may differ, they generally result from combinations of simple, constitutive mechanisms of membrane curvature generation. These include (but are not limited to) membrane insertion, membrane scaffolding, curvature sensing, molecular crowding, and membrane wrapping. We show in each case how these different membrane curvature generation mechanisms coordinate to induce topological changes in membranes