Dynamic Mechanochemical feedback between curved membranes and BAR protein self-organization

Abstract

In many physiological situations, BAR proteins interact with, and reshape, pre-existing curved membranes, contributing to essential cellular processes. However, the non-equilibrium and timedependent process of reshaping, and its dependence on initial membrane shape, remains largely unknown. Here we explain, both experimentally and through modelling, how a BAR protein dynamically interacts with mechanically bent lipid membranes. We capture protein binding to curved membranes, and characterize a variety of dynamical reshaping events depending on membrane shape and protein arrangement. The events can be generally understood by an isotropic-to-nematic phase transition, in which low curvature templates with isotropic protein orientation progress towards highly curved lipid tubes with nematic protein arrangement. Our findings also apply in cells, where mechanical stretch triggers BAR-protein-membrane interactions that enable potential mechanotransduction mechanisms. Our results characterize and broaden the reshaping processes of BAR proteins on mechanically constrained membranes, demonstrating the interplay between membrane mechanical stimuli and BAR protein response.

A theory of ordering of elongated and curved proteins on membranes driven by density and curvature

“…However, it does not say anything about how the proteins, with a given density or orientational distributions, affect the shape of the underlying membrane. This situation is examined experimentally and computationally elsewhere 32 , where the present model is coupled with one of membrane dynamics.…”

“…In the present work, membrane curvature is taken as given. In a companion paper, we couple the model presented here with one for a deformable membrane to study the mechano-chemistry of membrane reshaping by BAR proteins 32 . In Section 1, the entropy of elongated proteins on the membrane is obtained by adapting to 2D a recent theory by Nascimento et.…”

Sensing their plasma membrane curvature allows migrating cells to circumvent obstacles

“…Several studies have attempted to decipher the reasons behind the diversity of curvaturesensing proteins 29 , highlighting their role in membrane reorganization downstream of extracellular mechanical stimulation 30 . Here, by using leukocytes, which polarize and generate a leading-edge in an adhesion-independent manner, we take a cell centric approach to demonstrate a new role for membrane topography in de-stabilizing lamellipodia for efficient navigation.…”