Abstract
The closure of gaps within epithelia is crucial to maintain its integrity during biological processes such as wound healing and gastrulation. Depending on the distribution of extracellular matrix, gap closure occurs through assembly of multicellular actin-based contractile cables or protrusive activity of border cells into the gap. Here we show that the supracellular actomyosin contractility of cells near the gap edge exerts sufficient tension on the surrounding tissue to promote closure of non-adherent gaps. Using traction force microscopy, we observe that cell-generated forces on the substrate at the gap edge first point away from the centre of the gap and then increase in the radial direction pointing into the gap as closure proceeds. Combining with numerical simulations, we show that the increase in force relies less on localized purse-string contractility and more on large-scale remodelling of the suspended tissue around the gap. Our results provide a framework for understanding the assembly and the mechanics of cellular contractility at the tissue level.
Highlights
The closure of gaps within epithelia is crucial to maintain its integrity during biological processes such as wound healing and gastrulation
Studying the closure of gaps and discontinuities within multicellular sheets is of great interest because of the important role that it plays in various biological processes such as embryogenesis, tissue morphogenesis and wound healing
We have previously reported that keratinocytes migrating on micropatterned lines can form suspended epithelial bridges that rely on contractile actin bundles over regions devoid of extracellular matrix (ECM) proteins to close gaps and maintain epithelial integrity[16]
Summary
The closure of gaps within epithelia is crucial to maintain its integrity during biological processes such as wound healing and gastrulation. We have previously reported that keratinocytes migrating on micropatterned lines can form suspended epithelial bridges that rely on contractile actin bundles over regions devoid of ECM proteins to close gaps and maintain epithelial integrity[16] As both cell crawling and actin purse-string mechanisms co-exist during gap closure, this can induce discontinuities in the actin organization around the gap because of the presence of protrusive extensions as well as contractile actin bundles[7,10,17,18]. In addition to lamellipodia extensions towards the gap, the assembly of discontinuous supracellular contractile actin cables connected to the substrate through focal adhesions promotes efficient wound closure by compressing the underlying substrate[19] Because such mechanisms rely on cell–substrate interactions, it is difficult to understand how gaps close in situations where the ECM is heterogeneous and/or poorly adherent. By using micropatterned substrates[20], we study the closure of circular gaps devoid of ECM protein and functionalized h h h
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