The Cell Adaptation Time Sets a Minimum Length Scale for Patterned Substrates

The structure and dynamics of tissue cultures depend strongly on the physical and chemical properties of the underlying substrate. Inspired by previous advances in the context of inorganic materials, the use of patterned culture surfaces has been proposed as an effective way to induce space-dependent properties in cell tissues. However, cells move and diffuse, and the transduction of external stimuli to biological signals is not instantaneous. Here, we show that the fidelity of patterns to demix tissue cells depends on the relation between the diffusion (tau(D)) and adaptation (tau) times. Numerical results for the self-propelled Voronoi model reveal that the fidelity decreases with tau/tau(D), a result that is reproduced by a continuum reaction-diffusion model. Based on recent experimental results for single cells, we derive a minimal length scale for the patterns in the substrate that depends on tau/tau(D) and can be much larger than the cell size.