Persistence-Driven Durotaxis: Generic, Directed Motility in Rigidity Gradients

Abstract

Cells move differently on substrates with different elasticities. In particular, the persistence time of their motion is higher on stiffer substrates. We show that this behavior will result in a net transport of cells directed up a soft-to-stiff gradient. Using simple random walk models with controlled persistence and stochastic simulations, we characterize this propensity to move in terms of the durotactic index measured in experiments. A one-dimensional model captures the essential features of this motion and highlights the competition between diffusive spreading and linear, wavelike propagation. Since the directed motion is rooted in a non-directional change in the behavior of individual cells, the motility is a kinesis rather than a taxis. Persistence-driven durokinesis is generic and may be of use in the design of instructive environments for cells and other motile, mechanosensitive objects.

A Rho-GTPase based model explains spontaneous collective migration of neural crest cell clusters

“…3a). We did not find any experimental data of T p for NCCs, but human mammary epithelial cells have a persistence time of T p ∼ 10 min [37] while fibroblasts exhibit a range of persistence times between 15 to 120 minutes [43,44].…”

Mechanosensing of matrix by stem cells: From matrix heterogeneity, contractility, and the nucleus in pore-migration to cardiogenesis and muscle stem cells in vivo

“…Importantly, theory and simulation recently demonstrated that any gradient in persistent migration (e.g. less persistent on soft matrix and more persistent on stiff matrix) is sufficient to cause directed migration [35]. Observing durotaxis of stem cells in vivo is challenging, but critical to elucidating the role durotaxis plays in physiological differentiation and discovering if durotaxis contributes to disease states.…”

Topotaxis of active Brownian particles

“…[31,32]. Because of the nonequilibrium nature of active particles, local asymmetries in the environment can be leveraged to create a drift; these particles have been demonstrated to perform chemotaxis [33,34], durotaxis [35], and phototaxis [36]. Furthermore, topographical cues, such as those obtained in the presence of arrays of asymmetric posts [37,38] and ratchets consisting of asymmetric potentials [39][40][41] or asymmetric channels [42][43][44][45], have been shown to produce a directional bias in the motion of active particles reminiscent of those observed for cells.…”