28 June 2024
Katie Bentley
The Francis Crick Institute
London, UK
Humans and many other organisms use feedback between movement and sensing known as 'sensorimotor coordination' or 'active perception' to inform better decision-making. We move to improve the quality of what is sensed. Despite cells highly plastic, dynamic and protrusive shapes, the role of local movement (cell shape changes) in improving the quality of sensed information via signaling/mechanotransduction receptors to improve cellular decision-making has received very little attention. Perhaps in part due to cell signalling and cell movement largely being studied in isolated biology fields using very different assays.
We are currently developing new tools to study the role of movement-signalling coupling (cellular active perception) in cell decisions: 1) spatiotemporal cell simulations to predict ways to systematically de-couple and identify the key interactions driving feedback; 2) information theory metrics, e.g. transfer entropy, to measure the level of coupling and information flow (collaborating with Pedro Mediano, Imperial) and 3) micropatterning in vitro testbeds to validate and measure the level of sensorimotor coupling used by cells to make specific decisions (in collaboration with Chris Chen, BU). We are also collaborating to test the theories in vivo. I will describe this theory and growing toolsets, our latest results focussing on endothelial cells as well as preliminary studies extending to other protrusive cells (fibroblasts and glial/immune cells).
Our first proof of concept in silico/in vivo studies indicate that endothelial cells form dynamic protrusions, which confer positive feedback and bistable properties to signaling via sensorimotor feedback, to speed up collective notch patterning decisions, improving vascular network cellularity and branching topology [1]. We now have first evidence in vitro that protrusions indeed move receptors such that internal cell activation is enhanced and growing evidence this mechanism is harnessed to improve sensing of both pro- and, counter intuitively anti-migratory signalling pathways, suggesting cell shape movements may be required for perception of a wide variety of environmental signals, constituting a pervasive cellular "basal cognition" process with much more yet to be discovered.