Mathematical Optimisation of Actin-Driven Protrusion Formation in Eukaryotic Chemotaxis

SamuelJohnson

University of Oxford

"Mathematical Optimisation of Actin-Driven Protrusion Formation in Eukaryotic Chemotaxis"

In eukaryotic chemotaxis, cells extend and retract transient actin-driven protrusions at their membrane. These protrusions facilitate both the detection of external chemical gradients and directional movement via the formation of focal adhesions with the extracellular matrix. While extensive experimental work has characterised how protrusive activity varies with a range of environmental parameters, the mechanistic principles governing these relationships remain poorly understood. Here, we model the extension of actin-based protrusions in chemotaxis mathematically as an optimisation problem, wherein cells must balance the detection of external chemical gradients with the energetic cost of protrusion formation. The model highlights energetic efficiency in movement as a major predictor of phenotypic variation amongst motile cell populations, successfully reproducing experimentally observed but previously non-understood patterns of protrusive activity across a range of biological systems. Additionally, we leverage the model to generate novel predictions regarding cellular responses to environmental perturbations, providing testable hypotheses for future experimental work.
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