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

Glioblastoma invasion critically limits therapeutic outcomes, yet the physical principles that govern directional cell migration remain poorly understood. In particular, the degree to which protrusive forces are aligned or cancel each other, and how this governs migration efficiency, have remained unquantified. Here, we introduce mechanical polarity, a quantitative descriptor that captures the alignment of protrusive and adhesive forces driving migration. By integrating time-lapse imaging of the glioblastoma-derived cells with a coarse-grained biophysical model incorporating catch- and slip-bond kinetics, we analyzed motility on fibronectin- and laminin-coated substrates. In our model, the extracellular matrix (ECM) is treated as an external boundary condition that modulates adhesion dynamics, distinct from intrinsic cellular mechanics. We demonstrate that while protrusive activity remains similar across environments, the fibronectin-fitted model exhibited less stable effective adhesion dynamics that led to poorly coordinated protrusions and significant force cancellation, thereby reducing net displacement. These differences are not fully captured by conventional descriptors of protrusion activity but are reflected in mechanical polarity. Conversely, laminin promotes stable adhesions and the alignment of protrusive forces, a state characterized by high mechanical polarity. Our results support mechanical polarity as a candidate physical descriptor linking molecular adhesion kinetics to cell-scale migration stability. This framework provides a quantitative basis for understanding force coordination in glioblastoma cell motility and offers a physical basis for strategies to suppress invasive behavior.