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Crawling cells can close wounds without purse strings or signaling.

ABSTRACT: When a gash or gouge is made in a confluent layer of epithelial cells, the cells move to fill in the "wound." In some cases, such as in wounded embryonic chick wing buds, the movement of the cells is driven by cortical actin contraction (i.e., a purse string mechanism). In adult tissue, though, cells apparently crawl to close wounds. At the single cell level, this crawling is driven by the dynamics of the cell's actin cytoskeleton, which is regulated by a complex biochemical network, and cell signaling has been proposed to play a significant role in directing cells to move into the denuded area. However, wounds made in monolayers of Madin-Darby canine kidney (MDCK) cells still close even when a row of cells is deactivated at the periphery of the wound, and recent experiments show complex, highly-correlated cellular motions that extend tens of cell lengths away from the boundary. These experiments suggest a dominant role for mechanics in wound healing. Here we present a biophysical description of the collective migration of epithelial cells during wound healing based on the basic motility of single cells and cell-cell interactions. This model quantitatively captures the dynamics of wound closure and reproduces the complex cellular flows that are observed. These results suggest that wound healing is predominantly a mechanical process that is modified, but not produced, by cell-cell signaling.

SUBMITTER: Lee P

PROVIDER: S-EPMC3053312 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Crawling cells can close wounds without purse strings or signaling.

Lee Pilhwa P Wolgemuth Charles W CW

PLoS computational biology 20110310 3

When a gash or gouge is made in a confluent layer of epithelial cells, the cells move to fill in the "wound." In some cases, such as in wounded embryonic chick wing buds, the movement of the cells is driven by cortical actin contraction (i.e., a purse string mechanism). In adult tissue, though, cells apparently crawl to close wounds. At the single cell level, this crawling is driven by the dynamics of the cell's actin cytoskeleton, which is regulated by a complex biochemical network, and cell si ...[more]

PMID: 21423710

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Project description:OBJECTIVE:China is emerging as an increasingly important player in the global development space, but may be less bound to compacts that aim to curb political preferencing and therefore may produce less yield in terms of impact toward Sustainable Development Goals. This research tests the hypothesis that the disproportionate aid allocation to the birth regions of the current African political leaders that applies to some sectors more than others. DESIGN:We applied a two-part model to first estimate the probability that a region receives an aid project. Then when at least one aid project is present in a leader's birth region, we estimated the mean amount of aid the region received. SETTING:This analysis covers 699 subnational units (first administrative level) across 44 African countries over 2000-2014. These administrative units were compiled into a region year panel resulting in 10,485 observations. RESULTS:Birth regions of the current political leader are significantly more likely than the average of all of the regions to receive education (1.3 percentage points), social infrastructure and services (1.2 percentage points), and energy aid (1.7 percentage points). No significant association was found between aid flows to the birth region of the current political leader in the agriculture, communication, education, government, health or transportation sectors. Within the education sector, the coefficients for birth region are positive in both parts and statistically significant. Both the probability of aid allocation and the amount of aid conditional on any projects increase in the birth region of the current political leader. CONCLUSIONS:This sector-specific analysis provides a more nuanced picture of Chinese aid than previous analyses that determine the presence of political preference according to aggregate aid flows. The sectors where political preferencing exists are also those sectors that are typically associated with limited counterfactual-based program evaluation. We present evidence that demonstrates the importance of disaggregating aid flows in order to support a new policy framework designed to target the Sustainable Development Goals.

Project description:BACKGROUND:All animals have mechanisms for healing damage to the epithelial sheets that cover the body and line internal cavities. Epithelial wounds heal either by cells crawling over the wound gap, by contraction of a super-cellular actin cable ("purse string") that surrounds the wound, or some combination of the two mechanisms. Both cell crawling and purse string closure of epithelial wounds are widely observed across vertebrates and invertebrates, suggesting early evolution of these mechanisms. Cnidarians evolved ~600 million years ago and are considered a sister group to the Bilateria. They have been much studied for their tremendous regenerative potential, but epithelial wound healing has not been characterized in detail. Conserved elements of wound healing in bilaterians and cnidarians would suggest an evolutionary origin in a common ancestor. Here we test this idea by characterizing epithelial wound healing in live medusae of Clytia hemisphaerica. RESULTS:We identified cell crawling and purse string-mediated mechanisms of healing in Clytia epithelium that appear highly analogous of those seen in higher animals, suggesting that these mechanisms may have emerged in a common ancestor. Interestingly, we found that epithelial wound healing in Clytia is 75 to >600 times faster than in cultured cells or embryos of other animals previously studied, suggesting that Clytia may provide valuable clues about optimized healing efficiency. Finally, in Clytia, we show that damage to the basement membrane in a wound gap causes a rapid shift between the cell crawling and purse string mechanisms for wound closure. This is consistent with work in other systems showing that cells marginal to a wound choose between a super-cellular actin cable or lamellipodia formation to close wounds, and suggests a mechanism underlying this decision. CONCLUSIONS:1. Cell crawling and purse string mechanisms of epithelial wound healing likely evolved before the divergence of Cnidaria from the bilaterian lineage ~ 600mya 2. In Clytia, the choice between cell crawling and purse string mechanisms of wound healing depends on interactions between the epithelial cells and the basement membrane.

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Crawling cells can close wounds without purse strings or signaling.

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Crawling cells can close wounds without purse strings or signaling.

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