In their environment, cells must cope with mechanical stresses constantly. Among these, nanoscale deformations of plasma membrane induced by substrate nanotopography are now largely accepted as a biophysical stimulus influencing cell behavior and function. However, the mechanotransduction cascades involved and their precise molecular effects on cellular physiology are still poorly understood.
Scientists from our Institute (Pierre Morsomme, David Alsteens) and UNamur (Pierre-Henri Renard) have been pooling their expertise in cell biology and sharing their techniques in an attempt to decipher certain cellular mechanisms. One of them is to understand how cells interact with the tiny reliefs appearing on the extracellular matrix. Their work has just resulted in a major publication in Science Advances, with Benjamin Ledoux, former LIBST doctoral student, as first author.
Using homemade fluorescent nanostructured cell culture surfaces, we explored the role of Bin/Amphiphysin/Rvs (BAR) domain proteins as mechanosensors of plasma membrane geometry. Our data reveal that distinct subsets of BAR proteins bind to plasma membrane deformations in a membrane curvature radius–dependent manner. Furthermore, we show that membrane curvature promotes the formation of dynamic actin structures mediated by the Rho GTPase CDC42, the F-BAR protein CIP4, and the presence of PI(4,5)P2. In addition, these actin-enriched nanodomains can serve as platforms to regulate receptor signaling as they appear to contain interferon-γ receptor (IFNγ-R) and to lead to the partial inhibition of IFNγ-induced JAK/STAT signaling.
Read the article published in Science Advances