Mechanical polarity links adhesion-tuned protrusions to directional stability in glioblastoma cell migration

Glioblastoma invasion critically limits therapeutic outcomes, and understanding the physical principles that govern cell motility is essential for developing effective therapies. Here, to clarify the mechanical links between cell adhesion, protrusions, and migration, we analyzed glioblastoma-derived cells migrating on fibronectin- and laminin-coated extracellular matrix (ECM) substrates using time-lapse imaging and mathematical modeling. We quantified cell motility on each ECM and constructed a coarse-grained biophysical model that incorporates catch- and slip-bond kinetics. We treated the ECM as an external boundary condition that modulates adhesion dynamics, distinct from the intrinsic mechanical parameters of the cell. The model reproduced ECM-dependent differences in cell motility. The results suggest that adhesions and protrusion elongation on fibronectin are less stable than on laminin, and opposing forces between protrusions reduce net displacement more strongly on fibronectin than on laminin, leading to less coordinated tensile forces. Based on these results, we establish mechanical polarity, defined as an imbalance of protrusion- and adhesion-mediated forces that drive directional migration, as a quantifiable physical principle of cell protrusion and migration. This principle likely extends beyond glioblastoma biology, providing a generalizable mechanism that links adhesion dynamics to migration stability and offering a physical basis for strategies to suppress invasive cell behavior.