Abstract
A series of traction force microscopy experiments involving pairs of keratocytes migrating on compliant substrates were analyzed. We observed several instances where keratocytes that are about to collide turn before they touch. We term this phenomenon collision avoidance behavior and we propose that the turning is caused by the substrate mediated elastic interactions between the cells. A multipole analysis of the cell traction reveals that the left-right symmetry of the keratocyte traction pattern is broken during collision avoidance events. The analysis further shows that the cell migration direction reorients before the principal traction dipoles as the cells turn. Linear elasticity theory is used to derive the cell-cell interaction energy between pairs of keratocytes. The traction force applied by each cell is modeled as a two points (dipole) or three points (tripod) force model. We show that both models predict that cells that are about to collide in a head-on manner will turn before touching. The tripod model is further able to account for the quadrupole components of the traction force profile that we observed experimentally. Also, the tripod model proposes a mechanism that may explain why cells tend to scatter with a finite angle after a collision avoidance event. A relationship between the scattering angle and the traction force quadrupole moment is also established. Dynamical simulations of migrating model cells are further used to explain the emergence of other cell pair trajectories that we observed experimentally.
Highlights
The ability of cells to reorient in response to changes in the physical properties of their environment is well known [1, 2]
For cells that move toward another in a near head-on collision manner, we hypothesized that the cells will often turn and scatter without touching, due to substrate mediated elastic interactions
Our experiments show that the frequency of this phenomenon depends on the substrate stiffness: Fewer collisions are observed on the softer of the two substrate
Summary
The ability of cells to reorient in response to changes in the physical properties of their environment is well known [1, 2]. Capillary endothelial cells will reorient perpendicular to applied strain [3], and cells attached to flexible surfaces exhibit durotaxis [4], in which they move towards regions of increased rigidity. Cancer metastasis is promoted by the tendency of abnormal cells to migrate towards stiffer regions of the extracellular matrix (ECM) at the edge of tumors [5]. Most of the recent research emphasis has been on the reorientation of cells in sheets to external stresses [6] or the guidance cues provided by substrate stiffness [4, 5].
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