Alignment of cellular motility forces with tissue flow as a mechanism for efficient wound healing.
Recent experiments have shown that spreading epithelial sheets exhibit a long-range coordination of motility forces that leads to a buildup of tension in the tissue, which may enhance cell division and the speed of wound healing. Furthermore, the edges of these epithelial sheets commonly show finger-like protrusions whereas the bulk often displays spontaneous swirls of motile cells. To explain these experimental observations, we propose a simple flocking-type mechanism, in which cells tend to align their motility forces with their velocity. Implementing this idea in a mechanical tissue simulation, the proposed model gives rise to efficient spreading and can explain the experimentally observed long-range alignment of motility forces in highly disordered patterns, as well as the buildup of tensile stress throughout the tissue. Our model also qualitatively reproduces the dependence of swirl size and swirl velocity on cell density reported in experiments and exhibits an undulation instability at the edge of the spreading tissue commonly observed in vivo. Finally, we study the dependence of colony spreading speed on important physical and biological parameters and derive simple scaling relations that show that coordination of motility forces leads to an improvement of the wound healing process for realistic tissue parameters.
Center for Theoretical Biological Physics and Department of Physics, University of California at San Diego, La Jolla, CA 92093-0374, USA.
Markus
M
Basan
Jens
J
Elgeti
Edouard
E
Hannezo
Wouter-Jan
WJ
Rappel
Herbert
H
Levine
D002465:Cell Movement / Q000502:physiology*; D003198:Computer Simulation; D004847:Epithelial Cells / Q000502:physiology*; D008954:Models, Biological; D013314:Stress, Mechanical; D014945:Wound Healing / Q000502:physiology*