Abstract
Cells perform directed motion in response to external stimuli that they detect by sensing the environment with their membrane protrusions. Precisely, several biochemical and biophysical cues give rise to tactic migration in the direction of their specific targets. Thus, this defines a multi-cue environment in which cells have to sort and combine different, and potentially competitive, stimuli. We propose a non-local kinetic model for cell migration in which cell polarization is influenced simultaneously by two external factors: contact guidance and chemotaxis. We propose two different sensing strategies, and we analyze the two resulting transport kinetic models by recovering the appropriate macroscopic limit in different regimes, in order to observe how the cell size, with respect to the variation of both external fields, influences the overall behavior. This analysis shows the importance of dealing with hyperbolic models, rather than drift-diffusion ones. Moreover, we numerically integrate the kinetic transport equations in a two-dimensional setting in order to investigate qualitatively various scenarios. Finally, we show how our setting is able to reproduce some experimental results concerning the influence of topographical and chemical cues in directing cell motility.
Highlights
Cell migration is a fundamental mechanism in a huge variety of processes, such as wound healing, angiogenesis, tumor stroma formation, and metastasis
Due to the lack of mathematical models looking at the interplay between chemotaxis and contact guidance from a non-local perspective and the biological relevance of this topic, in this paper we develop a non-local kinetic model describing the combined effect of these two directional cues on the choice of the direction of cell migration
We have proposed a kinetic model for describing cell migration in a multicue environment
Summary
Cell migration is a fundamental mechanism in a huge variety of processes, such as wound healing, angiogenesis, tumor stroma formation, and metastasis. During these processes, cells sense the environment and respond to external stimuli orienting their direction of motion toward specific targets. ECM stiffness can be counted as a biophysical cue, as well as the collagen fiber alignment The latter is shown to stimulate contact guidance (Friedl and Brocker 2000; Friedl 2004), i.e., the tendency of cells to migrate by crawling on the fibers and following the directions imposed by them. We take into account non-local sensing of both cues, since cells extend their protrusions in order to sense the environmental stimuli
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