Nano-Mechano-Biology on living cell membranes

Research over the last two decades has provided compelling evidence that the physical principle of molecular spatiotemporal organization orchestrates information flow at the cell surface. In particular, clustering has emerged as a ubiquitous organizational principle across a myriad of different receptors that bind to distinct ligands, expressed in many cell types and performing different functions. What are the fundamental principles that govern receptor nanoclustering? How are nanoclusters assembled (and dissembled)? What is their role? How are they regulated with such a high fidelity and universality?

We are intensively studying the nature of these nanoclusters using different forms of super-resolution imaging and high-density single molecule imaging in living cells combined with multiple labelling strategies, state-of-art fluorescent probes, molecular and cell biology. We combine these approaches with tools that allow us to modulate the mechanical environment of cells using nano-stretching devices, lipid bilayers of variable viscosity and, 3D-hydrogels, all compatible with single molecule imaging. To enquire on the role of the plasma membrane and its mechanical properties, we are currently investigating how membrane tension and its spatial propagation contribute to the compartmentalization of the plasma membrane. For this, we combine our tools with mechano-sensitive fluorescent probes and push the limits of fluorescence lifetime imaging to uncover the existence of tensional nano-compartments at the plasma membrane and assess whether they enable localized and timely receptor nanocluster signalling.