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

Reproducció del document publicat a: https://doi.org/10.1038/s41467-021-26591-3 In many physiological situations, BAR proteins reshape membranes with pre-existing curvature (templates), contributing to essential cellular processes. However, the mechanism and the biological implications of this reshaping process remain unclear. Here we show, both experimentally and through modelling, that BAR proteins reshape low curvature membrane templates through a mechanochemical phase transition. This phenomenon depends on initial template shape and involves the co-existence and progressive transition between distinct local states in terms of molecular organization (protein arrangement and density) and membrane shape (template size and spherical versus cylindrical curvature). Further, we demonstrate in cells that this phenomenon enables a mechanotransduction mode, in which cellular stretch leads to the mechanical formation of membrane templates, which are then reshaped into tubules by BAR proteins. Our results demonstrate the interplay between membrane mechanics and BAR protein molecular organization, integrating curvature sensing and generation in a comprehensive framework with implications for cell mechanical responses. This work was supported by the Spanish Ministry of Science and Innovation (PGC2018-099645-B-I00 to X.T., PID2019-110949GB-I00 to M.A., BFU2016-79916-P and PID2019-110298GB-I00 to P.R.-C.), the Spanish Ministry of Economy and Competitiveness/FEDER (BES-2016-078220 to C.T., the European Commission (H2020-FETPROACT-01-2016-731957), the European Research Council (Adv-883739 to X.T., CoG-681434 to M.A.), the Generalitat de Catalunya (2017-SGR-1602 to X.T. and P.R.-C., 2017-SGR-1278 to M.A.), the prize “ICREA Academia” for excellence in research to P.R.-C. and to M.A., Fundació la Marató de TV3 (201936-30-31 and 201903-30-31-32), and “la Caixa” Foundation (Agreement LCF/PR/HR20/52400004). IBEC and CIMNE are recipients of a Severo Ochoa Award of Excellence from the MINECO. We would like to thank all the members of P. Roca-Cusachs, X. Trepat, and M. Arroyo laboratories for technical assistance and discussions. We thank M. Pons, X. Menino, M.G. Parajo, M.-A. Rodriguez, N. Castro, R. Sunyer, I. Granero, V. González, the Unitat de Criomicroscòpia Electrònica (Centres Científics i Tecnològics de la Universitat de Barcelona, CCiTUB), and the MicroFabSpace and Microscopy Characterization Facility, Unit 7 of ICTS “NANBIOSIS” from CIBER-BBN at IBEC, for their excelle