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Issue 12, 2015
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Coupling between apical tension and basal adhesion allow epithelia to collectively sense and respond to substrate topography over long distances

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Abstract

Epithelial sheets fold into complex topographies that contribute to their function in vivo. Cells can sense and respond to substrate topography in their immediate vicinity by modulating their interfacial mechanics, but the extent to which these mechanical properties contribute to their ability to sense substrate topography across length scales larger than a single cell has not been explored in detail. To study the relationship between the interfacial mechanics of single cells and their collective behavior as tissues, we grew cell-sheets on substrates engraved with surface features spanning macroscopic length-scales. We found that many epithelial cell-types sense and respond to substrate topography, even when it is locally nearly planar. Cells clear or detach from regions of local negative curvature, but not from regions with positive or no curvature. We investigated this phenomenon using a finite element model where substrate topography is coupled to epithelial response through a balance of tissue contractility and adhesive forces. The model correctly predicts the focal sites of cell-clearing and epithelial detachment. Furthermore, the model predicts that local tissue response to substrate curvature is a function of the surrounding topography of the substrate across long distances. Analysis of cell–cell and cell–substrate contact angles suggests a relationship between these single-cell interfacial properties, epithelial interfacial properties, and collective epithelial response to substrate topography. Finally, we show that contact angles change upon activation of oncogenes or inhibition of cell-contractility, and that these changes correlate with collective epithelial response. Our results demonstrate that in mechanically integrated epithelial sheets, cell contractility can be transmitted through multiple cells and focused by substrate topography to affect a behavioral response at distant sites.

Graphical abstract: Coupling between apical tension and basal adhesion allow epithelia to collectively sense and respond to substrate topography over long distances

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Publication details

The article was received on 25 Sep 2015, accepted on 06 Oct 2015 and first published on 20 Oct 2015


Article type: Paper
DOI: 10.1039/C5IB00240K
Citation: Integr. Biol., 2015,7, 1611-1621
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    Coupling between apical tension and basal adhesion allow epithelia to collectively sense and respond to substrate topography over long distances

    K. E. Broaders, A. E. Cerchiari and Z. J. Gartner, Integr. Biol., 2015, 7, 1611
    DOI: 10.1039/C5IB00240K

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