Abstract
The wide range of epithelial cell shapes reveals the complexity and diversity of the intracellular mechanisms that serve to construct their morphology and regulate their functions. Using mechanosensitive steps, epithelial cells can sense a variety of different mechanochemical stimuli and adapt their behavior by reshaping their morphology. These changes of cell shape rely on a structural reorganization in space and time that generates modifications of the tensional state and activates biochemical cascades. Recent studies have started to unveil how the cell shape maintenance is involved in mechanical homeostatic tasks to sustain epithelial tissue folding, identity, and self-renewal. Here, we review relevant works that integrated mechanobiology to elucidate some of the core principles of how cell shape may be conveyed into spatial information to guide collective processes such as epithelial morphogenesis. Among many other parameters, we show that the regulation of the cell shape can be understood as the result of the interplay between two counteracting mechanisms: actomyosin contractility and intercellular adhesions, and that both do not act independently but are functionally integrated to operate on molecular, cellular, and tissue scales. We highlight the role of cadherin-based adhesions in force-sensing and mechanotransduction, and we report recent developments that exploit physics of liquid crystals to connect cell shape changes to orientational order in cell aggregates. Finally, we emphasize that the further intermingling of different disciplines to develop new mechanobiology assays will lead the way toward a unified picture of the contribution of cell shape to the pathophysiological behavior of epithelial tissues.
Highlights
Epithelial cells can sense a variety of different mechanochemical stimuli and adapt their behavior by reshaping their morphology
We highlight the role of cadherin-based adhesions in force-sensing and mechanotransduction, and we report recent developments that exploit physics of liquid crystals to connect cell shape changes to orientational order in cell aggregates
The field of mechanobiology has emerged at the interface of biology, engineering, and physics based on the recognition that physical forces and changes in the mechanical properties of cells and tissues contribute to development, cell differentiation, physiology, and disease.[20]
Summary
Living cells must change their shape dynamically during many important physiological processes, such as division,[28] migration,[29] and differentiation.[30]. Eukaryotic cell shape changes are mainly determined by the spatial reorganization of each cytoskeletal component (actin microfilaments, microtubules, and intermediate filaments), which form altogether a dynamic and responsive network.[33,34]. An interaction between the intermediate filament network and actin stress fibers was recently reported in keratinocytes, which regulates their matrix rigidity sensing and downstream signal transduction.[49]. Ventral stress fibers, which are considered as the main major force-generating actomyosin bundles in migrating cells, are connected to the microenvironment through focal adhesions that are the primary site of contact with the extracellular matrix (ECM). Adherens junctions form an adhesion belt that encircles each of the interacting epithelial cells, while a contractile bundle of actin filaments runs along the cytoplasmic surface of the junctional plasma membrane. Even if the cytoskeletal contraction is an important part of the regulation of cell shape changes, cell–substrate interactions play a key role in mechanosensing mechanisms leading to a cellular adaptation via cell shape changes.[61]
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