Boundary crossing in epithelial wound healing.
Tirrell, David A.
Date of Issue2010
School of Materials Science and Engineering
The processes of wound healing and collective cell migration have been studied for decades. Intensive research has been devoted to understanding the mechanisms involved in wound healing, but the role of cell-substrate interactions is still not thoroughly understood. Here we probe the role of cell-substrate interactions by examining in vitro the healing of mono layers of human corneal epithelial (HCE) cells cultured on artificial extra cellular matrix (aECM) proteins. We find that the rate of wound healing is dependent on the concentration off ibronectin-derived (RGD) cell adhesion lig and sin the aECM substrate. The wound closure rate varies nearly six fold on the substrates examined, despite the fact that the rates of migration and proliferation of individual cells show little sensitivity to the RGD concentration (which varies 40 fold). To explain this apparent contradiction, we study collective migration by means of a dynamic Monte Carlo simulation. The cells in the simulation spread, retract, and proliferate with probabilities obtained from a simple phenomenon logical model. The results indicate that the overall wound closure rate is determined primarily by the rate at which cells cross the boundary between the Aecm protein and the matrix deposited under the cell sheet.
Proceedings national academy of sciences
© 2010 National Academy of Sciences. This is the author created version of a work that has been peer reviewed and accepted for publication by Proceedings National Academy of Sciences, National Academy of Sciences. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: http://dx.doi.org/10.1073/pnas.1008291107.