Abstract
Cell migration is a highly integrated process and basic to many biological functions ranging from development to immune response and wound healing, to metastasis in cancer. For cells to migrate, they must generate and transduce traction forces to their environment, however, no technology to date has provided a high throughput solution for measuring these traction forces. Here we present a new assay for measuring cellular contractile forces employing robust multiwall culture plates: Using a 96-well plate format, we fabricate soft (∼1-10 kPa) elastic silicone rubbers with embedded fiduciary particles; by measuring the cell-induced deformation of these particles we calculate the cellular traction stresses and work using Fourier transform cytometry. We utilize this system to quantify the traction mechanics underlying cellular migration in several diseased settings including cancer metastasis, induced epithelial to mesenchymal transition (EMT), and aging; in all instances, we find significant changes in the contractile stresses and work, suggesting that contractile force screening may become a valuable biophysical diagnostic addition. This 96-well format and the use of a non-degrading soft silicone rubber create a simple and stable assay, and we anticipate that this technology will be of broad utility in diverse quantitative biological and health sciences.
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