Biology subjects

Le Roux, A.-L.

Publications and source records attributed to Le Roux, A.-L..

2 recordsLinked to original sources

bioRxiv2021

The force loading rate drives cell mechanosensing through both reinforcement and fluidization

Cell response to force regulates essential processes in health and disease. However, the fundamental mechanical variables that cells sense and respond to remain unclear. Here we show that the rate of force application (loading rate) drives mechanosensing, as predicted by a molecular clutch model. By applying dynamic force regimes to cells through substrate stretching, optical tweezers, and atomic force microscopy, we find that increasing loading rates trigger talin-dependent mechanosensing, leading to adhesion growth and reinforcement, and YAP nuclear localization. However, above a given threshold the actin cytoskeleton undergoes fluidization and softens, decreasing loading rates and preventing reinforcement. By stretching rat lungs in vivo, we show that a similar phenomenon occurs at the organ level. Our results show that cell sensing of external forces and of passive mechanical parameters (like tissue stiffness) can be understood through the same mechanisms, driven by the properties under force of the mechanosensing molecules involved.

biophysics↗

bioRxiv2020

Dynamic Mechanochemical feedback between curvedmembranes and BAR protein self-organization

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.

biophysics↗