Basement membrane turnover controls cell shape

The regulation of 3D cell shape is a fundamental problem of life. In multicellular tissues, cell shape emerges through the balance of forces inside and outside the cell. In epithelia, the basement membrane (BM) is the first extracellular barrier that cells sense biochemically and mechanically. Despite this, little is known about how BM mechanical properties are regulated and how they impact cell shape. Through mathematical modeling, we show that the stress relaxation time of the BM can regulate cell shape. Using molecular dynamics simulations, we show that the stress relaxation time of a collagen IV network can be inferred from the lifetime of collagen IV molecules. To measure collagen IV lifetime in vivo, we develop a fluorescent timer reporter for collagen IV and show that perlecan modifies collagen IV lifetime. This cross-disciplinary approach establishes a multiscale framework to probe matrix turnover, and its regulation and function in cell shape control.