Fig. 1: Cyclic change in substrate rigidity regulates cell migration on soft substrates.

a Cells exhibit sluggish movement on substrates possessing a Young’s modulus lower than 4 kPa. Particularly, hMSCs display limited migratory activity on soft substrates with a Young’s modulus around 1.6 kPa, while demonstrating efficient migration on rigid substrates with a Young’s modulus of ~13.0 kPa. The far-right panels show the trajectories of ~20 randomly selected migrating cells for each condition over 12 h. The far-left panels were created in BioRender. Z, Y. (2025) https://BioRender.com/ysxwnvq. b–e Time series of images of hMSC on the PYP hydrogels with different mechanical properties. The bottom-right panels show the trajectories of ~20 randomly selected migrating cells for each condition over 12 h. Times are indicated in hour:minute:second. Scale bar is 50 µm for all panels. f–h Average migration distance, average migration speed and mean square displacement (MSD) of hMSCs on the PYP hydrogels with different mechanical properties. The smooth, linear trends in the population-averaged plots for distance (f) and MSD (h) are emergent properties that result from averaging the asynchronous, intermittent movements of many individual cells. In f–h, n = 204, 202, 224, 207, 218, and 219 (1 min cycle, 5 min cycle, 10 min cycle, 2.2 kPa, 1.6 kPa, and 13.0 kPa) cells were examined, each from 3 independent experiments. In g, *** = p < 0.01, unpaired, two-tailed t-test. i, j Time series of images and average migration distance of hMSCs on the PYP hydrogels with fast cyclic rigidity change (transitioning between 2.2 kPa and 1.6 kPa) in the first 6 h and static rigidity (Young’s modulus of ~2.2 kPa) in the last 6 h. Times are indicated in hour:minute:second. Scale bar is 50 µm. In j, n = 176 cells were examined from 3 independent experiments. In f, h, and j, data are presented as mean values (central line) +/- standard deviation (shaded region). Source data are provided as a Source Data file.