Cellular guidance by chemical or physical signals is essential for many life processes and usually relies on sophisticated biological processes that are still partially elucidated. Microfluidic experiments and mechanical modeling has revealed that the choice for cells to orient themselves against or in the direction of a flow can result from a simple physical bias. They have worked with  keratocytes, cells that form the scale of fishes, and whose morphology is characterized by broad  flat “front” and a compact protruding front  “back”. A simplified model of a cell with a hemispherical back and a flat rectangular front allows to quantitatively calculate the forces that the flow exerts on each edge. The resulting force stabilizes the cells with a large rear edge against the flow, like a roly-poly that stays upright because of its heavy bottom edge. The researchers’ model successfully predicted the experimentally observed orientation for each cell without adjusting parameter. It is an elegant example where a characterized biological behavior does not result from specialized molecular sensors and a complex cascade of internal biosignals to reorient the cell, but from a simple passive physical bias.

https://www.pnas.org/doi/10.1073/pnas.2210379119

A– Keratocytes descending a flow, the white arrow indicates the direction of the stream. B– Cell morphology seen in 3D by confocal microscopy, with a bulbous back edge and a flat, thin front edge. C– Cell modeling with a hemisphere at the back (red) and a flat rectangle at the front (brown) D– The torques resulting from flow on cell front (red arrow) and cell front (brown arrow) stabilize upstream orientation of cell with larger rear edge, like the torque resulting from gravity stabilizes the standing position of roly-poly toys with large bottom edge. 

This paper was commented on in CNRS (link)