Asamataxis: A cooperative relayed migration in response to subsurface inhomogeneity leads to long-range self-patterning of cells

Cells self-organize to give patterns that are essential for tissue functioning. While the effects of biochemical and mechanical cues are relatively well studied, the role of stiffness inhomogeneity on cellular patterning is unexplored. Using a rigid structure embedded in soft polyacrylamide (PAA) gel, we show that such mechanical inhomogeneity leads to long-range self-organized cellular patterns. Our results reveal that this patterning depends on cellular traction and cell morphology. Depending on a suitable combination of cellular morphology and traction, the information about the presence of embedded structure gets relayed outward. In response to this relay, the cells reorient their axis and migrate towards the embedded structure leading to the observed long-range (20-35 cell length) patterning. To predict the possibility of pattern formation, we present a dimensionless number ′?′ combining the governing parameters. We have also shown that the pattern can be tailor-made by pre-designing sub-surface structures, a potential tool for tissue engineering. This mechanism of directed migration driven long-range pattern formation in response to mechanical inhomogeneity may be involved during several pathophysiological conditions, a proposition that needs further investigation.