Cell Monolayers Sense Curvature by Exploiting Active Mechanics and Nuclear Mechanoadaptation

This review appeared in the February 2022 edition of the BioAFM Journal Club — a monthly email brief highlighting leading-edge research and the latest discoveries supported by Bruker BioAFM technology.

Early development in many organisms involves the folding of cell monolayers into 3D curved structures, such as invaginations and wave-like morphologies in developing tissues. While the influence of topography on development at the cellular and subcellular scale has been studied in detail, the mechanistic and local curvature factors remain unclear.

In this article, AFM was used to study the curvature, structure and mechanics of epithelial cell monolayers grown on corrugated polyacrylamide hydrogels.

By engineering wave-like corrugated hydrogels with a finite amplitude and thickness, the authors demonstrated that concave (valleys) and convex (crests) curvatures affect epithelial cell monolayers. The curvature of the substrate affects the thickness of the epithelial layers, which reaches local maxima in the concave regions and appears to induce a flat apical configuration in the crest areas. Interestingly, the curvature does not influence the overall architecture of the monolayers, which successfully adapts to the corrugated matrices without resulting in changes to cell shape or global actin expression. The authors propose and verify a model suggesting that membrane-nucleus interactions influence nuclear morphometrics, such as nuclear deformation and offsetting, relative to changes in the local curvature. In addition, patterns of cellular densities could be correlated to the spatial distribution of YAP – a well-known mechanosensitive transcription factor. The results further suggest that nuclear lamin expression, chromatin condensation, and cell proliferation are modulated by the substrate curvature. The study identifies nuclear mechanoadaptation and active cell mechanics as key mechanistic regulators of epithelial cell monolayers on large-scale substrate curvatures.

      _{KEY TERMS:}

• Active Cell Mechanics; Computational Biophysics; Epithelial Cell Monolayers; Membrane Biophysics; Substrate Curvatures