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Tissue fusion over nonadhering surfaces

  1. Pascal Silberzana,b,2
  1. aLaboratoire Physico-Chimie Curie, Institut Curie, Centre de Recherche, Paris Sciences et Lettres Research University, Centre National de la Recherche Scientifique, Université Pierre et Marie Curie, Sorbonne Universités, 75248 Paris, France
  2. bLaboratoire PhysicoChimie Curie, Institut Curie, Equipe labellisée Ligue Contre le Cancer, 75248 Paris, France

  1. Edited by Robert H. Austin, Princeton University, Princeton, NJ, and approved June 19, 2015 (received for review January 20, 2015)

Significance

Tissue fusion is a frequent and important event in embryonic development during which two facing identical tissues meet and bridge collectively over a gap before merging into a continuous structure. Illustrations of tissue fusion include the formation of the palate or epithelial wound healing. In vivo fusion events, particularly in embryonic development, often involve the purse-string contraction of a pluricellular actomyosin cable present at the free edge. By studying the fusion of a monolayer over imprinted nonadherent domains, we provide evidence and characterize the purse-string mechanism in the situation where cells do not develop adhesions with their underlying substrate. A model that also involves active epithelial fluctuations describes well the experimental observations.

Abstract

Tissue fusion eliminates physical voids in a tissue to form a continuous structure and is central to many processes in development and repair. Fusion events in vivo, particularly in embryonic development, often involve the purse-string contraction of a pluricellular actomyosin cable at the free edge. However, in vitro, adhesion of the cells to their substrate favors a closure mechanism mediated by lamellipodial protrusions, which has prevented a systematic study of the purse-string mechanism. Here, we show that monolayers can cover well-controlled mesoscopic nonadherent areas much larger than a cell size by purse-string closure and that active epithelial fluctuations are required for this process. We have formulated a simple stochastic model that includes purse-string contractility, tissue fluctuations, and effective friction to qualitatively and quantitatively account for the dynamics of closure. Our data suggest that, in vivo, tissue fusion adapts to the local environment by coordinating lamellipodial protrusions and purse-string contractions.

Footnotes

  • ↵1V.N., M.D., and G.D. contributed equally to this work.

  • ↵2To whom correspondence may be addressed. Email: pascal.silberzan{at}curie.fr or philippe.marcq{at}curie.fr.

  • Author contributions: M.D., P.M., and P.S. designed research; V.N., M.D., G.D., H.G.Y., O.C.-E., and P.M. performed research; V.N., M.D., G.D., H.G.Y., O.C.-E., P.M., and P.S. analyzed data; and V.N., M.D., G.D., H.G.Y., O.C.-E., P.M., and P.S. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1501278112/-/DCSupplemental.

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