Substrate mediated interaction between pairs of keratocytes: Multipole traction force models describe their migratory behavior

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.

A model explaining environmental stiffness-dependent migration of fibroblasts with a focus on maturation of intracellular structures

“…Numerous mechanistic models have been proposed to describe cell migration. Focusing on ones that consider the interaction with the surrounding environment, synchronized beating of cardiomyocytes 23,24 and circumvention of interference between motile keratocytes 23,24 have been analyzed by modeling stress fibers as a force dipole. Focusing further on the effect of substrate stiffness on more normal proliferative cells such as fibroblasts used in the present study, cells were approximated to be composed of a set of springs and dampers mimicking the actin cytoskeleton 2,3 , and then cell movement was predicted from force balance.…”

Collective States of Active Particles With Elastic Dipolar Interactions

“…The overall motility of spatially separated cells is expected to depend on cell-cell mechanical interactions. This is revealed by experimental observations of substrate stiffness-dependent interactions of pairs of motile cells [23,24].…”

Coarse-grained modeling of cell division in 3D: influence of density, medium viscosity, and inter-membrane friction on cell growth and nearest neighbor distribution

“…Understanding mechanobiology of cellular systems is crucial to many facets of cellular behavior including growth (1), stem cell differentiation (2,3), embryonic morphogenesis in general (4,5), and cell migration and taxis (6)(7)(8)(9)(10)(11)(12)(13). Cancer cells are also known to have purely mechanical markers (12,(14)(15)(16) and thus mechanical properties have emerged as a potential new target for cancer drug development (15,16).…”

“…As a new approach to model mechanobiology Palmieri et al have recently introduced a (2D) phase-field model (8,11). Phase-field models are typically used in modeling materials and pattern formation (45)(46)(47), and they have recently been also applied to biomembranes (48,49).…”