Matrix stress relaxation promotes glioblastoma cell migration in a ligand-specific manner

Increasing evidence suggests that the behavior of cancer cells is largely regulated by the mechanical properties of the microenvironment. Here, we investigated the influence of substrate viscoelasticity and the type of adhesion ligand on the migration, morphology, and expression of mechanotransduction-related genes in LN-229 glioblastoma cells. Polyacrylamide hydrogels with similar storage moduli but different loss moduli were used to selectively analyze the role of stress relaxation. The migration of individual cells was analyzed using the time-lapse method. Additionally, a morphological analysis and an evaluation of gene expression were conducted. We observed that the effect of substrate viscoelasticity on LN-229 cells migration is highly dependent on the type of adhesion ligand. Between others, the increase in the loss modulus on substrates coated with type I collagen led to an increase in speed, net displacement, and a shift in migration strategy towards more organized persistent random walk-type movement. In turn, on laminin, increased substrate viscosity induced broad activation of mechanotransduction genes. The results obtained indicate that the viscoelasticity of ECM is not a universal promoter of GBM invasion but rather acts as a modulating factor in the behavior of cells in a manner dependent on the molecular context of adhesion.