Model for HGF/SF-induced collective motility patterns during the healing process.

<p>HGF/SF dramatically alters the morpho-dynamics of the healing wound: from a simple model, in which the front cells lead the healing in constant acceleration, to a more elaborate model in which cells in different distances from the wound lead a coordinated increased motility along with spatio-temporal phenotypic EMT-MET based collective cell motility dynamics. Untreated DA3 front layers cells are larger, more elliptical and move faster (marked by wider arrows) than cells located behind demonstrating a homogeneous motility pattern during the wound healing process (<i>Phases 1</i> and <i>2</i>). During post wound closure (<i>Phase 3</i>), all cells decelerate, shrink and round up regardless of their position. HGF/SF treatment leads to the emergence of dramatic different cell motility patterns: at the beginning, front cells are larger, more elliptical and move faster than distant cells. Throughout <i>Phase 1</i>, distant cells become larger, more elliptical and gradually join the rapid motion by accelerating layer by layer. These morphology changes and gradual acceleration continues during <i>Phase 2</i>, were distant cells maintain a higher velocity toward the wound than cells located closer to the wound edge. Finally, post wound closure (<i>Phase 3</i>), front cells shrink, round up and halt, while distant cells gradually decelerate, and change morphology in a similar manner. It is hypothesized that accelerated proliferation at the leading edge is the answer for the untreated cells gap mystery presented in the text. It is hypothesized that in treated cells proliferation occurs more intensively, but is spread approximately equally throughout the monolayer.