Exploration of Curvature\nand Stiffness Dual-Regulated\nBreast Cancer Cell Motility by a Motor-Clutch Model and Cell Traction\nForce Characterization

The migration of breast cancer cells is the main cause\nof death\nand significantly regulated by physical factors of the extracellular\nmatrix (ECM). To be specific, the curvature and stiffness of the ECM\nwere discovered to effectively guide cell migration in velocity and\ndirection. However, it is not clear what the extent of effect is when\nthese dual-physical factors regulate cell migration. Moreover, the\nmechanobiology mechanism of breast cancer cell migration in the molecular\nlevel and analysis of cell traction force (CTF) are also important,\nbut there is a lack of systematic investigation. Therefore, we employed\na microfluidic platform to construct hydrogel microspheres with an\nindependently adjustable curvature and stiffness as a three-dimensional\nsubstrate for breast cancer cell migration. We found that the cell\nmigration velocity was negatively correlated to curvature and positively\ncorrelated to stiffness. In addition, curvature was investigated to\ninfluence the focal adhesion expression as well as the assignment\nof F-actin at the molecular level. Further, with the help of a motor-clutch\nmathematical model and hydrogel microsphere stress sensors, it was\nconcluded that cells perceived physical factors (curvature and stiffness)\nto cause changes in CTF, which ultimately regulated cell motility.\nIn summary, we employed a theoretical model (motor-clutch) and experimental\nstrategy (stress sensors) to understand the mechanism of curvature\nand stiffness regulating breast cancer cell motility. These results\nprovide evidence of force driven cancer cell migration by ECM physical\nfactors and explain the mechanism from the perspective of mechanobiology.