Project: The regulation of mechanosensing in healthy and atherosclerotic vascular smooth muscle cells
Vascular smooth muscle cells (VSMCs) play a central role in the onset and progression of many cardiovascular diseases, from atherosclerosis to vascular injury, where their migration, matrix secretion, or degradation functions are deregulated. Enhanced matrix stiffness causes a switch of VSMC from a contractile to a synthetic phenotype. This switch is significantly enabled by the formation of podosomes, integrin-rich adhesive, mechanically protrusive structures at the matrix interface of the plasma membrane. Podosomes are also mechanosensitive: matrix stiffness affects the number of podosomes and their degradative properties in a variety of cell types. However, details of mechanical sensing in VSMC remain unclear. This project will use mechanical stimulation (pressure, stiffness, stretch), biomechanical characterisation (AFM, Nanoindentaion), cellular force measurements (nanopillars, FRET tension sensors) as well as (live) super-resolution microscopy to investigate the mechanical regulation of VSMC phenotypic switching.