Curvature-driven feedback on aggregation-diffusion of proteins in lipid bilayers

TL;DR

This paper develops a comprehensive model for protein aggregation on lipid bilayers, incorporating membrane bending, protein diffusion, and aggregation, to understand how these factors influence membrane-protein interactions and pattern formation.

Contribution

It introduces a novel coupled framework that combines lipid flow, membrane bending, protein entropy, and explicit aggregation potential, extending previous models to better predict membrane protein patterns.

Findings

Aggregation influences membrane curvature and protein pattern formation.

Coupled diffusion and aggregation alter membrane-protein interaction landscapes.

Model predictions align with observed protein aggregation behaviors in membranes.

Abstract

Membrane bending is an extensively studied problem from both modeling and experimental perspectives because of the wide implications of curvature generation in cell biology. Many of the curvature generating aspects in membranes can be attributed to interactions between proteins and membranes. These interactions include protein diffusion and formation of aggregates due to protein-protein interactions in the plane of the membrane. Recently, we developed a model that couples the in-plane flow of lipids and diffusion of proteins with the out-of-plane bending of the membrane. Building on this work, here, we focus on the role of explicit aggregation of proteins on the surface of the membrane in the presence of membrane bending and diffusion. We develop a comprehensive framework that includes lipid flow, membrane bending, the entropy of protein distribution, along with an explicit aggregation potential and derive the governing equations for the coupled system. We compare this framework to the Cahn-Hillard formalism to predict the regimes in which the proteins form patterns on the membrane. We demonstrate the utility of this model using numerical simulations to predict how aggregation and diffusion, when coupled with curvature generation, can alter the landscape of membrane-protein interactions.