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Am J Physiol Cell Physiol 293: C1327-C1337, 2007. First published August 8, 2007; doi:10.1152/ajpcell.00001.2007
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MUSCLE CELL BIOLOGY AND CELL MOTILITY

Roles of wound geometry, wound size, and extracellular matrix in the healing response of bovine corneal endothelial cells in culture

Silvina Grasso,1 Julio A. Hernández,2 and Silvia Chifflet1

1Departamento de Bioquímica, Facultad de Medicina, and 2Sección Biofísica, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay

Submitted 1 January 2007 ; accepted in final form 6 August 2007

It has classically been accepted that the healing of narrow wounds in epithelia occurs by the formation of a contractile actin cable, while wide wounds are resurfaced by lamellipodia-dependent migration of border cells into the denuded area. To further investigate the general validity of this idea, we performed systematic experiments of the roles of wound geometry, wound size, and extracellular matrix (ECM) in wound healing in monolayers of bovine corneal endothelial cells, a system shown here to predominantly display any of the two healing mechanisms according to the experimental conditions. We found that, in this system, it is the absence or presence of the ECM on the wound surface that determines the specific healing mode. Our observations demonstrate that, independent of their size and geometry, wounds created maintaining the ECM heal by migration of cells into the wound area, while ECM removal from the wound surface determines the predominant formation of an actin cable. While the latter mechanism is slower, the actin cable permits the maintainance of the epithelial phenotype to a larger extent during the healing process, as also confirmed by our finding of a more conserved localization of cadherin and vinculin. We also introduce a model that simulates experimental findings about the dynamics of healing mechanisms, both for the maintenance or removal of the ECM on the wound surface. The findings of this study may contribute to the understanding of physiological and pathological aspects of epithelial wound healing and to the design of therapeutic strategies.

epithelial wound healing; actin cable; lamellipodial crawling; dynamic model



Address for reprint requests and other correspondence: S. Chifflet, Dept. de Bioquímica, Facultad de Medicina, Gral Flores 2125, Montevideo 11800, Uruguay (e-mail: schiffle{at}mednet.org.uy)







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