The migration of breast cancer cells is the main cause
of death
and significantly regulated by physical factors of the extracellular
matrix (ECM). To be specific, the curvature and stiffness of the ECM
were discovered to effectively guide cell migration in velocity and
direction. However, it is not clear what the extent of effect is when
these dual-physical factors regulate cell migration. Moreover, the
mechanobiology mechanism of breast cancer cell migration in the molecular
level and analysis of cell traction force (CTF) are also important,
but there is a lack of systematic investigation. Therefore, we employed
a microfluidic platform to construct hydrogel microspheres with an
independently adjustable curvature and stiffness as a three-dimensional
substrate for breast cancer cell migration. We found that the cell
migration velocity was negatively correlated to curvature and positively
correlated to stiffness. In addition, curvature was investigated to
influence the focal adhesion expression as well as the assignment
of F-actin at the molecular level. Further, with the help of a motor-clutch
mathematical model and hydrogel microsphere stress sensors, it was
concluded that cells perceived physical factors (curvature and stiffness)
to cause changes in CTF, which ultimately regulated cell motility.
In summary, we employed a theoretical model (motor-clutch) and experimental
strategy (stress sensors) to understand the mechanism of curvature
and stiffness regulating breast cancer cell motility. These results
provide evidence of force driven cancer cell migration by ECM physical
factors and explain the mechanism from the perspective of mechanobiology.