Substrate Stress Relaxation Regulates Cell Migration

Mechanical stimuli from the extracellular matrix (ECM) play an essential role in regulating important biological processes including cell spreading, migration, proliferation, and differentiation. However, these studies typically use elastic materials as substrates, whereas natural ECM is a viscoelastic material and exhibits stress relaxation properties. Here, we investigate the influence of substrate stress relaxation on cell migration properties by using an alginate-based materials system with adjustable stress relaxation rates. We find that two-dimensional (2D) collective cell migration, three-dimensional (3D) single cell migration and three-dimensional (3D) collective cell migration are all enhanced when cells were cultured in gels with fast relaxation. However, even though the two-dimensional (2D) single cell average migration speed initially increases with the increase of stress relaxation rates, it later decreases. These findings highlight stress relaxation as a key factor regulating cell migration