Role of BAR domain proteins and downstream signalling at plasma membrane deformations induced by colloidal particles
(2023)
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- Abstract
- In their environment, cells have to cope with mechanical stresses constantly. Among those, cell deformation due to the presence of nanotopographical features is now largely accepted as a biophysical stimulus influencing cellular functions. Especially, nanotopography controls crucial behaviours including stem cell differentiation and multicellular organisation, which have considerable implications in tissue engineering and regenerative medicine. However, the mechanotransduction cascades involved in nanotopography recognition and their precise molecular effects on cellular physiology are still poorly understood. To bridge the gap, BAR domain proteins are attractive candidates as their intrinsic properties position them right at the interface between membranes and signalling. Yet, their ability to translate plasma membrane curvature into molecular responses is only superficially explored. Here, using homemade fluorescent nanostructured cell culture surfaces, we investigated the role of 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. Interestingly, distinct cellular processes involving BAR domain proteins seem to be primed at these sites of high membrane curvature. We focused on one of them, the local actin cytoskeleton polymerisation. We demonstrated 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, independently of clathrin. Furthermore, these actin-enriched nanodomains appear to serve as platforms regulating membrane receptor signalling. In particular, we provide evidence that interferon-γ receptor is enriched in these nanodomains and that its signalling through JAK/STAT is partially inhibited. Altogether, these findings may be key for understanding the effects of nanotopography on cellular behaviour in biological contexts as diverse as development, cancer progression or for the design of biocompatible materials.
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Ledoux, B. (2023). Role of BAR domain proteins and downstream signalling at plasma membrane deformations induced by colloidal particles. https://hdl.handle.net/2078.5/106378