Keratocytes migrate against flow with a roly-poly-like mechanism.

While cell migration can be directed by various mechanical cues such as force, deformation, stiffness, or flow, the associated mechanisms and functions may remain elusive. Single cell migration against flow, repeatedly reported with leukocytes, is arguably considered as active and mediated by integrin mechanotransduction, or passive and determined by a mechanical bias. Here, we reveal a phenotype of flow mechanotaxis with fish epithelial keratocytes that orient upstream or downstream at shear stresses around tens of dyn cm-2. We show that each cell has an intrinsic orientation that results from the mechanical interaction of flow with its morphology. The bulbous trailing edge of a keratocyte generates a hydrodynamical torque under flow that stabilizes an upstream orientation, just as the heavy lower edge of a roly-poly toy generates a gravitational torque that stabilizes an upright position. In turn, the wide and flat leading edge of keratocytes destabilizes upstream orientation, allowing the existence of two distinct phenotypes. To formalize these observations, we propose a simple mechanical model that considers keratocyte morphology as a hemisphere preceded by a wide thin sheet. Our findings show that this model can recapitulate the phase diagram of single cell orientation under flow without adjustable parameters. From a larger perspective, this passive mechanism of keratocytes flow mechanotaxis implies a potential absence of physiological function and evolution-driven process.

Appreciating the role of cell shape changes in the mechanobiology of epithelial tissues.

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.