Bio Focus: Wound healing: Mind the gap, pull strings
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LETIN
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VOLUME 40 • SEPTEMBER 2015
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www.mrs.org/bulletin
cytoskeletal features), or traction force microscopy (to assess force dipole orientations across regions of positive and negative curvature). Forces tended to be perpendicular to edges with positive curvature, indicating cell crawling activity, and tangential to edges with negative curvature, indicating purse-string dynamics. In a telling experiment, the actomyosin cable running along the gap edge was site-specifically severed by laser ablation, thereby mechanically disentangling regions of positive and negative curvature. Under this condition, tissue edges advanced at similar rates across regions of both positive and negative curvature. With an intact actin cable, however, regions with negative curvature moved relatively faster. Complementary experiments with drug inhibitors were able to isolate each closure mechanism by inactivating either purse-string closure or cell crawling independently. This revealed that purse-string closure speed depends on gap curvature (moving faster toward the gap with more negative curvature, and exhibiting edge retraction with positive curvature), while cell crawling speed remained largely unaffected by curvature. The experimental insights obtained by the researchers allowed them to develop a mathematical model describing gap closure dynamics. The resulting simulations closely agreed with experimental results (see Figure c). The model incorporates the relative influence of cell crawling, purse-string action, and tissue boundary curvature in a general way such that in addition to accurately describing gap closure in the present study, the model further predicts relative contributions of crawling and purse-string mechanisms for other modes of motility such as cell extrusion and tissue expansion. Describing motility dynamics through such an insightful mechanistic framework is an important step toward more fully understanding epithelial tissues as complex natural biomaterials, and should ultimately allow improved designs of synthetic biomaterials that can interface with such tissues to accelerate wound healing in biomedical contexts. Lukmaan Bawazer
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