BPS2026 – Membrane morphologies arising from multi-conformational protein states

It has long been established by both theory and experiment that cells actively sculpt the shapes of membranes by utilizing curvature-stabilizing proteins that modulate the effective elastic properties of the membrane. While it has also been known that many membrane proteins may transition between alternative conformational states, the implications of these conformational changes on membrane shaping are largely undetermined. Using continuum-based physical modeling, we explore how membrane proteins with multiple conformations can collectively shape biological membranes. We show that the conformational flexibility of such proteins may lead to emergent behaviors, such as mechanical bistability of the membrane and collective organization. In order to derive the emergent membrane morphologies, we introduce the “Piecewise-CMC” surface representation: a novel curvature-based shape discretization scheme that allows for efficient depiction of membrane geometries, based on constant-mean-curvature shape primitives. We utilize the Piecewise-CMC method in order to demonstrate that membranes embedded with multi-conformation proteins can spontaneously adopt non-uniform shapes, driven by spatial patterning of protein conformational states or by redistribution of the proteins in the membrane plane. Our general mechanism highlights how multi-state proteins may collectively orchestrate large-scale morphological changes, providing a fundamental insight into the functional organization of diverse biological membrane systems, while the Piecewise-CMC algorithm may be useful for efficient modeling of membranal geometries in different systems.