Epithelial bridges maintain tissue integrity during collective cell migration

• DOI: 10.1038/nmat3814
• Publication Date: 2013-11-29T08:40:47Z
• Authors: Sri Ram Krishna V...; Hiroaki Hirata; Mui Hoon Nai; Agustı´ Brugués; Yusuke Toyama; Xavier Trepat; Chwee Teck Lim; Benoit Ladoux
• Keywords: Keratinocytes; 570; 0303 health sciences; Tissue Scaffolds; Surface Properties; [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph]; Fibrinogen; Biocompatible Materials; Elasticity; [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM]; Cell Line; Extracellular Matrix; 03 medical and health sciences; Cell Movement; Cell Adhesion; Humans; Dimethylpolysiloxanes

The ability of skin to act as a barrier is primarily determined by the efficiency of skin cells to maintain and restore its continuity and integrity. In fact, during wound healing keratinocytes migrate collectively to maintain their cohesion despite heterogeneities in the extracellular matrix. Here, we show that monolayers of human keratinocytes migrating along functionalized micropatterned surfaces comprising alternating strips of extracellular matrix (fibronectin) and non-adherent polymer form suspended multicellular bridges over the non-adherent areas. The bridges are held together by intercellular adhesion and are subjected to considerable tension, as indicated by the presence of prominent actin bundles. We also show that a model based on force propagation through an elastic material reproduces the main features of bridge maintenance and tension distribution. Our findings suggest that multicellular bridges maintain tissue integrity during wound healing when cell-substrate interactions are weak and may prove helpful in the design of artificial scaffolds for skin regeneration.