Fig. 8. A working model explaining that wound injury triggered Agrin microenvironment favors a productive healing program.

Briefly, Agrin sensitizes the wounded cells towards ECM rigidity, force recognition, and geometric constraints accounting for improved traction stress, elasticity, and cytoskeletal tension to promote enhanced fluid-like dynamic collective migration (blue arrows) over the wounded sites. Further, Agrin activates MMP12 as its downstream effector to upgrade the mechanoperception of keratinocytes and actomyosin integrity during keratinocyte migration. The cumulative outcome of an Agrin-driven mechanically competent wound healing micro-environment yields higher collective migration and wound closure via facilitating re-epithelization, optimal ECM deposition, and angiogenesis.