Out-of-equilibrium mechanochemistry and self-organization of fluid membranes interacting with curved proteins

The function of biological membranes is controlled by the interaction of the fluid lipid bilayer with various proteins, some of which induce or react to curvature. These proteins can preferentially bind or diffuse towards curved regions of the membrane, induce or stabilize membrane curvature and sequester membrane area into protein-rich curved domains. The resulting tight interplay between mechanics and chemistry is thought to control organelle morphogenesis and dynamics, including traffic, membrane mechanotransduction, or membrane area regulation and tension buffering. Despite all these processes are fundamentally dynamical, previous work has largely focused on equilibrium and a self-consistent theoretical treatment of the dynamics of curvature sensing and generation has been lacking. Here, we develop a general theoretical and computational framework based on a nonlinear Onsager’s formalism of irreversible thermodynamics for the dynamics of curved proteins and membranes. We develop variants of the model, one of which accounts for membrane curving by asymmetric crowding of bulky off-membrane protein domains. As illustrated by a selection of test cases, the resulting governing equations and numerical simulations provide a foundation to understand the dynamics of curvature sensing, curvature generation, and more generally membrane curvature mechano-chemistry

The plasma membrane as a mechanochemical transducer

Cells are constantly submitted to external mechanical stresses, which they must withstand and respond to. By forming a physical boundary between cells and their environment that is also a biochemical platform, the plasma membrane (PM) is a key interface mediating both cellular response to mechanical stimuli, and subsequent biochemical responses. Here, we review the role of the PM as a mechanosensing structure. We first analyse how the PM responds to mechanical stresses, and then discuss how this mechanical response triggers downstream biochemical responses. The molecular players involved in PM mechanochemical transduction include sensors of membrane unfolding, membrane tension, membrane curvature or membrane domain rearrangement. These sensors trigger signalling cascades fundamental both in healthy scenarios and in diseases such as cancer, which cells harness to maintain integrity, keep or restore homeostasis and adapt to their external environment. This article is part of a discussion meeting issue ‘Forces in cancer: interdisciplinary approaches in tumour mechanobiology’