Conserved mechanisms of repair: from damaged single cells to wounds in multicellular tissues

Abstract

The capacities to repair minor membrane holes in damaged single cells, and the more major damage sustained when a multicellular tissue is wounded, both involve a series of ancient and highly conserved processes. In this review, we discuss what is known about how the plasma membrane of a single cell and its underlying cortical cytoplasm are repaired following cell damage, and how multicellular wounds to the embryonic and adult skin are also able to heal. Pivotal for all these processes is the actin cytoskeleton and we draw analogies between the actin machineries that drive repair and those that appear to underlie several genetically tractable morphogenetic processes that occur during Drosophila and Caenorhabditis elegans embryogenesis.

A possible role for membrane depolarization in epithelial wound healing

“…The cellular events leading to the modifications of the actin cytoskeleton in the course of epithelial wound healing are complex and incompletely understood (26,56,62). As mentioned above (see Introduction), several factors participating in the initial stages of this response have been described.…”

“…Although the interruption of intercellular contacts may, in principle, play a role in triggering the repair response, a current view is that growth factor liberation by the injured cells specifically activates signaling pathways of the surviving neighboring cells (27,51,62). Also, an early Ca 2ϩ wave of short duration, propagated from the leading edge toward the center of the monolayer, has repeatedly been detected immediately after experimental wounds (27,51,55).…”

The Effects of Colloidal Nanotopography on Initial Fibroblast Adhesion and Morphology

“…Increasing adhesive interactions between fibroblasts and implant materials would be likely to result in fibrous encapsulation of the foreign body, especially if it were mobile [10]. However, colloidal topographies do offer potential applications for topical wound healing, where increased adhesive interactions would prove advantageous with respect to closure of wounds via actin contraction "purse-string" effects, especially with respect to the 50-nm-diameter colloids, or "zippering" effects, where fibroblast protrusions interact with neighboring elongations resulting in cell-cell contact and site closure, specifically in relation to the 20-nm-diameter colloidal substrates [47], [48]. Furthermore, materials enhanced using colloidal-based lithography techniques could be used to produce a substrate attractive to fibroblasts, which may offer a technique of rapid proliferation or granulation resulting in faster wound healing [11].…”

Biomimetic Delivery of Keratinocyte Growth Factor upon Cellular Demand for Accelerated Wound Healing in Vitro and in Vivo

“…The results are likely to depend on the type of wound (acute versus chronic) because chronic wounds display higher proteolytic activity [62][63][64] and may require higher concentrations of aprotinin for optimum fibrin degradation.…”