Enhanced chemotaxis through spatially-regulated absolute concentration robustness

Abstract

Chemotaxis, the directional motility of cells in response to spatial gradients of chemical cues, is a fundamental process behind a wide range of biological events, including the innate immune response and cancer metastasis. Recent advances in cell biology have shown that the protrusions that enable amoeboid cells to move are driven by the stochastic threshold crossings of an underlying excitable system. As a cell encounters a chemoattractant gradient, the size of this threshold is regulated spatially so that the crossings are biased towards the front of the cell. For efficient directional migration, cells must limit undesirable lateral and rear-directed protrusions. The inclusion of a control mechanism to suppress these unwanted firings would enhance chemotactic efficiency. It is known that absolute concentration robustness (ACR) exerts tight control over the mean and variance of species concentration. Here, we demonstrate how the coupling of the ACR mechanism to the cellular signaling machinery reduces the likelihood of threshold crossings in the excitable system. Moreover, we show that using the cell’s innate gradient sensing apparatus to direct the action of ACR to the rear, suppresses the lateral movement of the cells and that this results in improved chemotactic performance.

The emergence of a collective sensory response threshold in ant colonies

“…Mechanistically, thresholds in biological systems almost always emerge from a balance between two opposing forces: exciting and restoring electrical currents in excitable membranes 9 , excitatory and inhibitory neurons in neural networks 10 , or inter-region connections at the level of the entire brain 11 . Similar dynamical phenomena are also abundant in non-neural systems such as the immune system, cellular and microorganismal behavior, or intracellular signaling networks [12][13][14][15] .…”