Effect of substrate stiffness on friction in collective cell migration

Abstract

In collective cell migration, the motion results from forces produced by each cell and transmitted to the neighboring cells and to the substrate. Because inertia is negligible and the migration occurs over long time scales, the cell layer exhibits viscous behavior, where force and motion are connected by an apparent friction that results from the breaking and forming of adhesive bonds at the cell–cell and cell–substrate interfaces. Most theoretical models for collective migration include an apparent friction to connect force and motion, with many models making predictions that depend on the ratio of cell–cell and cell–substrate friction. However, little is known about factors that affect friction, leaving predictions of many theoretical models untested. Here, we considered how substrate stiffness and the number of adhesions affected friction at the cell–substrate interface. The experimental data were interpreted through prior theoretical models, which led to the same conclusion, that increased substrate stiffness increased the number of cell–substrate adhesions and caused increased cell–substrate friction. In turn, the friction affected the collective migration by altering the curvature at the edge of the cell layer. By revealing underlying factors affecting friction and demonstrating how friction perturbs the collective migration, this work provides experimental evidence supporting prior theoretical models and motivates the study of other ways to alter the collective migration by changing friction.

Temperature dependent model for the quasi-static stick–slip process on a soft substrate

“…41,46 Correspondingly, evidence has been provided that the friction experienced by cells is an increasing function of substrate stiffness. [47][48][49] Interestingly, this observation is in perfect agreement with the results obtained by means of the model here proposed for the stick-slip phenomenon on soft substrate, as discussed below. Anyway, a complete view on the motion of cells is not yet available, and many points remain to be clarified: cells propagate faster with increasing stiffness only up to optimal stiffness, 50 there are different cells migration modes to investigate, 51 wrinkles appear in bacterial biofilms growing on soft substrates, 52 and the cells motion shows a biphasic relation with substrate stiffness and friction.…”

MACC1-Induced Collective Migration Is Promoted by Proliferation Rather Than Single Cell Biomechanics

“…A further likely difference between the previous and the current study is the differential coupling of signaling cascades in both tumor entities, which may cause different downstream effects. On the other hand, SW480 and SW620 cells were stationary as isolated cells, potentially due to different cell surface friction compared to the glioblastoma cells [ 23 , 41 ], thus behaving highly differently from the beginning. Still, compared with the other studies, both mechanistic and functional, conducted in CRC, changes in migration are to be expected.…”

Hexanematic crossover in epithelial monolayers depends on cell adhesion and cell density

“…In MDCK-WT cells, in particular, the hexanematic crossover occurs at larger length scales compared to MDCK E-cad KO cells and the 6−fold symmetry inherited by the shape of individual cells persists up to clusters consisting approximately 3 to 13 cells, depending on the monolayer density. Interestingly, increasing the cell density has been reported to strengthen intercellular adhesion 41,42 , while decreasing the alignment of stress fibers 41 . Together with our observations, this suggests that, in epithelial layers, multiple physical and biochemical mechanisms could conspire toward consolidating hexatic order at small length scales.…”