Prediction of traction forces of motile cells.

When crawling on a flat substrate, living cells exert forces on it via adhesive contacts, enabling them to build up tension within their cytoskeleton and to change shape. The measurement of these forces has been made possible by traction force microscopy (TFM), a technique which has allowed us to obtain time-resolved traction force maps during cell migration. This cell 'footprint' is, however, not sufficient to understand the details of the mechanics of migration, that is how cytoskeletal elements (respectively, adhesion complexes) are put under tension and reinforce or deform (respectively, mature and/or unbind) as a result. In a recent paper, we have validated a rheological model of actomyosin linking tension, deformation and myosin activity. Here, we complement this model with tentative models of the mechanics of adhesion and explore how closely these models can predict the traction forces that we recover from experimental measurements during cell migration. The resulting mathematical problem is a PDE set on the experimentally observed domain, which we solve using a finite-element approach. The four parameters of the model can then be adjusted by comparison with experimental results on a single frame of an experiment, and then used to test the predictive power of the model for following frames and other experiments. It is found that the basic pattern of traction forces is robustly predicted by the model and fixed parameters as a function of current geometry only.

Time-dependent traction force microscopy for cancer cells as a measure of invasiveness.

The migration of tumor cells of different degrees of invasivity is studied, on the basis of the traction forces exerted in time on soft substrates (Young modulus∼10 kPa). It is found that the outliers of the traction stresses can be an effective indicator to distinguish cancer cell lines of different invasiveness. Here, we test two different epithelial bladder cancer cell lines, one invasive (T24), and a less invasive one (RT112). Invasive cancer cells move in a nearly periodic motion, with peaks in velocity corresponding to higher traction forces exerted on the substrate, whereas less invasive cells develop traction stresses almost constant in time. The dynamics of focal adhesions (FAs) as well as cytoskeleton features reveals that different mechanisms are activated to migrate: T24 cells show an interconnected cytoskeleton linked to mature adhesion sites, leading to small traction stresses, whereas less invasive cells (RT112) show a less-structured cytoskeleton and unmature adhesions corresponding to higher traction stresses. Migration velocities are smaller in the case of less invasive cells. The mean squared displacement shows super-diffusive motion in both cases with higher exponent for the more invasive cancer cells. Further correlations between traction forces and the actin cytoskeleton reveal an unexpected pattern of a large actin rim at the RT112 cell edge where higher forces are colocalized, whereas a more usual cytoskeleton structure with stress fibers and FAs are found for T24 cancer cells. We conjecture that this kind of analysis can be useful to classify cancer cell invasiveness.