Deformation gradients imprint the direction and speed of en masse fibroblast migration for fast healing

J Invest Dermatol. 2013 Oct;133(10):2471-2479. doi: 10.1038/jid.2013.184. Epub 2013 Apr 17.

Abstract

En masse cell migration is more relevant compared with single-cell migration in physiological processes of tissue formation, such as embryogenesis, morphogenesis, and wound healing. In these situations, cells are influenced by the proximity of other cells including interactions facilitated by substrate mechanics. Here, we found that when fibroblasts migrated en masse over a hydrogel, they established a well-defined deformation field by traction forces and migrated along a trajectory defined by field gradients. The mechanics of the hydrogel determined the magnitude of the gradient. For materials stiff enough to withstand deformation related to cellular traction forces, such patterns did not form. Furthermore, migration patterns functioned poorly on very soft matrices where only a minimal traction gradient could be established. The largest degree of alignment and migration velocity occurred on the gels with the largest gradients. Granulation tissue formation in punch wounds of juvenile pigs was correlated strongly with the modulus of the implanted gel, in agreement with in vitro en masse cell migration studies. These findings provide basic insight into the biomechanical influences on fibroblast movement in early wounds and relevant design criteria for the development of tissue-engineered constructs that aim to stimulate en masse cell recruitment for rapid wound healing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Cell Count
  • Cell Movement / physiology*
  • Extracellular Matrix / physiology
  • Female
  • Fibroblasts / cytology*
  • Fibroblasts / physiology*
  • Granulation Tissue / physiology
  • Humans
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Primary Cell Culture
  • Sepharose
  • Tissue Engineering / methods
  • Wound Healing / physiology*

Substances

  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Sepharose