Effect of matrix heterogeneity on cell mechanosensing.

Cells sense mechanical signals within the extracellular matrix, the most familiar being stiffness, but matrix stiffness cannot be simply described by a single value. Randomness in matrix structure causes stiffness at the scale of a cell to vary by more than an order of magnitude. Additionally, the extracellular matrix contains ducts, blood vessels, and, in cancer or fibrosis, regions with abnormally high stiffness. These different features could alter the stiffness sensed by a cell, but it is unclear whether the change in stiffness is large enough to overcome the noise caused by heterogeneity due to the random fibrous structure. Here we used a combination of experiments and modeling to determine the extent to which matrix heterogeneity disrupts the potential for cell sensing of a locally stiff feature in the matrix. Results showed that, at the scale of a single cell, spatial heterogeneity in local stiffness was larger than the increase in stiffness due to a stiff feature. The heterogeneity was reduced only for large length scales compared to the fiber length. Experiments verified this conclusion, showing spheroids of cells, which were large compared to the average fiber length, spreading preferentially toward stiff inclusions. Hence, the propagation of mechanical cues through the matrix depends on length scale, with single cells being able to sense only the stiffness of the nearby fibers and multicellular structures, such as tumors, also sensing the stiffness of distant matrix features.

Spatiotemporal force and motion in collective cell migration.

Cells move in collective groups in biological processes such as wound healing, morphogenesis, and cancer metastasis. How active cell forces produce the motion in collective cell migration is still unclear. Many theoretical models have been introduced to elucidate the relationship between the cell's active forces and different observations about the collective motion such as collective swirls, oscillations, and rearrangements. Though many models share the common feature of balancing forces in the cell layer, the specific relationships between force and motion vary among the different models, which can lead to different conclusions. Simultaneous experimental measurements of force and motion can aid in testing assumptions and predictions of the theoretical models. Here, we provide time-lapse images of cells in 1 mm circular islands, which are used to compute cell velocities, cell-substrate tractions, and monolayer stresses. Additional data are included from experiments that perturbed cell number density and actomyosin contractility. We expect this data set to be useful to researchers interested in force and motion in collective cell migration.