Cells communicate with other cells and their surrounding environment through multiple receptors, proteins and lipids located at the cell surface. Specific receptors recognise their ligands and upon binding to them, they rely this information to the cell interior by initiating signalling cascades that ultimate result in appropriate cell responses. Research over the last two decades has evidenced that aside from receptor expression, their spatial organisation within the plane of the membrane plays a crucial role for initiating cellular function. Importantly, this organisation occurs at multiple spatial scales, starting at the nanometre scale and being highly dynamic. These studies have provided unique insights on receptor spatiotemporal organisation and cell function but have been mostly performed in the absence of mechanical signals. Yet, cells in our body are exposed to different types of mechanical stimuli: shear stress in blood and lymph, irregular topographical cues of extracellular matrix fibres, changes in cell contractility and tension, etc. Components of the cell machinery such as the actin cytoskeleton, the glycocalyx matrix, and the lipid bilayer itself, sense these mechanical cues. How do mechanical stimuli affect the spatiotemporal organisation of receptors on the cell surface?; how these changes transduce to the cell interior to ultimately modulate cellular response? These are the two major questions that we addressed in NANO-MEMEC. Since the process of mechanical sensing and transduction starts at the molecular and nanoscale levels, a mechanistic understanding at the nanoscale is vital to further progress in the field. The overall objective of NANO-MEMEC has been thus to provide quantitative and mechanistic understanding on the role of mechanical stimuli and biochemical coupling in the spatiotemporal organisation of receptor nano-assemblies at the cell membrane. Our ambition has been to visualise, probe and quantify these processes at the relevant spatiotemporal scales with single molecule detection sensitivity within the whole complexity of the living cell. By doing so, NANO-MEMEC will open new frontiers of research by establishing membrane-based nano-mechanobiology as a novel mechanism that crucially contributes to signal transduction and cellular response. NANO-MEMEC poses fundamental questions to the field of cell membrane mechanobiology, but with an impact for society in the long run: receptor organisation is important for proper cell function, and any mis-regulation of this organisation will result in diseases including cancer, neurological disorders and auto-immune pathologies amongst others. Insight on how receptors organise and respond in the presence of mechanical stimuli will allow us to identify what, when and how it goes wrong to hopefully trigger the development of more targeted therapies to correct for these mis-functions.
