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

Abstract

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.

Not all (cells) who wander are lost: Upstream migration as a pervasive mode of amoeboid cell motility

“…It should be noted that the mechanism of M2 macrophage movement likely differs compared to other immune cell types, due to its abundant expression of Mac-1, but this remains an open area of investigation as to the direct mechanism. Keratinocytes: Recent work was the first to establish that the upstream migration mode of motility is not restricted only to immune cells as a certain sub-population of fish keratinocytes are able to crawl upstream on glass slides (Seveau de Noray et al, 2022). Although the keratinocytes preferentially migrated downstream, a sub-population with a prominent trailing edge were able to crawl upstream, as compared to those with a prominent leading-edge.…”

A high throughput cell stretch device for investigating mechanobiology in vitro

“…[8][9][10][11][12][13][14] Once applied, forces are translated via sensor-specific mechanotransduction pathways to initiate some of the most fundamental cell functions including transcription, 15 growth, 16 division, 17 polarity, 18 differentiation, 19 and migration. 7,[20][21][22] However, the absence of mechanosensation in cells can be as disruptive as whole organ dysfunction. [23][24][25] In addition, adaption mechanisms to mechanical stress may be employed by cells such as stress buffering, [26][27][28] persistent mechanical memory, [29][30][31][32][33][34] or reciprocal modification of the extracellular environment.…”