Emergent Collective Chemotaxis without Single-Cell Gradient Sensing

Abstract

Many eukaryotic cells chemotax, sensing and following chemical gradients. However, experiments have shown that even under conditions when single cells cannot chemotax, small clusters may still follow a gradient. This behavior has been observed in neural crest cells, in lymphocytes, and during border cell migration in Drosophila, but its origin remains puzzling. Here, we propose a new mechanism underlying this “collective guidance”, and study a model based on this mechanism both analytically and computationally. Our approach posits that contact inhibition of locomotion (CIL), where cells polarize away from cell-cell contact, is regulated by the chemoattractant. Individual cells must measure the mean attractant value, but need not measure its gradient, to give rise to directional motility for a cell cluster. We present analytic formulas for how cluster velocity and chemotactic index depend on the number and organization of cells in the cluster. The presence of strong orientation effects provides a simple test for our theory of collective guidance.

Cell-to-cell variation sets a tissue-rheology–dependent bound on collective gradient sensing

“…If this is the case, the effective rotational diffusion coefficient is just D r ∼ Ω 2 τ switch -so D r ∼ v 2 max τ switch /R 2 . By contrast, we have seen that in the absence of a collective aligning effect, rotational diffusion can be small or absent, depending on certain details about the underlying cell motility model [26].…”

“…When we keep a fixed cluster geometry, we choose to work with hexagonally-packed cell clusters, following our earlier work [26]. We illustrate clusters with Q = 1, 2, and 3 layers in Fig.…”

“…These cell-to-cell variations (CCV) can be persistent over timescales much larger than the typical motility timescale of the cell [25]. CCV has not been addressed in models of collective chemotaxis and it is not clear whether collective gradient sensing is limited by CCV or by stochastic receptor-ligand binding [7,8,[26][27][28][29][30].Using a combination of analytics and simulations, we show that unless CCV is tightly controlled, collective guidance of a cluster of cells is limited by these variations: gradient sensing is biased toward cells with intrinsically strong responses. This bias swamps the effects of stochastic ligand-receptor binding.…”

Collective gradient sensing and chemotaxis: modeling and recent developments

“…This will occur without any particular interactions within cells other than keeping the cluster tightly connected. In the context of collective cell migration, a specific minimal model including only this feature is discussed briefly in [64], and more extensively under the name “individual-based chemotaxis” in [65]; however, this is a well-known phenomenon in animal migration more generally, under the name of the “many wrongs principle” [66]. …”

“…One simple and straightforward approach is for each cell to polarize out from its neighbors, and pull proportional to the concentration it measures [8, 64]. As a result of a tug-of-war, the cluster will move toward higher concentration.…”