Dynamic rigidity changes enable rapid cell migration on soft substrates

Cell migration is crucial in various biological processes, regulated by surrounding rigidity. Studies under static conditions suggest migration favors rigid substrates, as softer substrates (<4 kPa) do not provide sufficient traction forces. Here we show that mesenchymal stem cells (MSCs) can overcome this limitation when exposed to rapid cyclic changes in substrate rigidity. Under dynamic conditions, cell traction forces progressively rise, promoting a swift mechanical turnover of focal adhesions. This adaptation obviates the need for cell polarity and the mechanochemical turnover of focal adhesions typically required for traditional mesenchymal-type migration. The rapid migration speed together with the shape evolution during migration can be adequately predicted by our theoretical model that considers the force balance under dynamic conditions. Our findings underscore the innate capacity of cells to navigate through fluctuating mechanical cues, highlighting a versatile cellular response mechanism for understanding cell behaviors under dynamic physiological or pathological conditions.