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Everett Price
Everett Price

Friction Vs Metrik - Timelapse

In this study, we conducted experiments to perturb the friction in cell monolayers. Following the equation that friction force is equal to Nkvτ, we hypothesized that increasing the substrate stiffness would increase the friction. The results were interpreted by comparison to two different theoretical models, the first by Garcia et al. predicting a biphasic relationship between velocity correlation length and speed, depending on the balance of viscosity and friction14, and the second by Alert et al. predicting that length scale λ is proportional to the size of a protrusion at the edge of the cell layer18.

Friction Vs Metrik - Timelapse


In summary, there are two possible mechanisms by which substrate stiffness affects friction. The first is the direct effect on variable k in the expression Nkvτ. The second is indirect and results from the active cell response to increased substrate stiffness by creating more and larger focal adhesions, thereby increasing the variable N. Both mechanisms lead to the same prediction, that increased substrate stiffness would increase the friction.

A central limitation of our study was that friction in the cell layer cannot be measured directly, meaning interpretation of the results was indirect. To mitigate this limitation, our study interpreted the experimental results through two prior models, built using different theoretical frameworks. The first model, by Garcia et al., was based on a combination of analytical theory for cells moving in clusters due to active cell forces and particle-based simulations14. The second model, by Alert et al., was based on a continuum model for an active polar fluid18. Although the second model has not yet been confirmed by experiments, predictions of the first model were verified by experiments performed by Garcia et al. Our experiments agree with the experiments of Garcia et al. and the predictions of both models, meaning that our data give the first experimental confirmation of predictions of the model by Alert et al. Additionally, the conclusions that came from interpreting our experimental data through the two models were the same, namely that increasing substrate stiffness increased the ratio of friction to viscosity. This information, together with our data showing no effect of substrate stiffness on E-cadherin, provides evidence that increasing substrate stiffness increased the friction between the migrating cell layer and the substrate.

For the mechanical confinement of cells, we previously developed an assay that places cells underneath a slab of PDMS held at a defined height above cover glass by micron-sized beads (Fig 1A) [14]. Previously, it was shown that the phenotypic transition to fast amoeboid (leader bleb-based) migration occurs most efficiently when cells are confined down to 3 μm [4]. Moreover, it has been shown that fast amoeboid cells transmit motive forces through non-specific friction, which can be modulated through surface coatings [6]. In our confinement assay, all surfaces are coated with 1% BSA to increase non-specific friction. Although Liu et al. demonstrated that several cell types can undergo this phenotypic transition, melanoma cells represent the best studied model of LBBM. Therefore, we have used melanoma A375-M2 cells for validating the Fiji/ImageJ-based plugin described here.

This is not to say that environmental policy for terrestrial systems, but there are fewer moving parts to manage. For example, a forest in the United States would likely not be an international jurisdiction case because the borders are permanent lines and national management does not overlap. However, at a state level, jurisdiction may overlap with potentially conflicting agendas. A critical difference in management strategies is preservation versus conservation. Preservation focuses on protecting nature from use and discourages altering the environment. Conservation, centers on wise-use practices that allow for proper human use of environments such as resource use for economic groups. One environmental group may believe in preservation, while one government agency may believe in conservation, creating friction amongst how the land should be used: timber harvest, public use, private purchasing, etc. 041b061a72


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