Quantifying traction stresses in adherent cells.

Contractile force generation plays a critical role in cell adhesion, migration, and extracellular matrix reorganization in both 2D and 3D environments. Characterization of cellular forces has led to a greater understanding of cell migration, cellular mechanosensing, tissue formation, and disease progression. Methods to characterize cellular traction stresses now date back over 30 years, and they have matured from qualitative comparisons of cell-mediated substrate movements to high-resolution, highly quantitative measures of cellular force. Here, we will provide an overview of common methods used to measure forces in both 2D and 3D microenvironments. Specific focus will be placed on traction force microscopy, which measures the force exerted by cells on 2D planar substrates, and the use of confocal reflectance microscopy, which can be used to quantify collagen fibril compaction as a metric for 3D traction forces. In addition to providing experimental methods to analyze cellular forces, we discuss the application of these techniques to a large range of biomedical problems and some of the significant challenges that still remain in this field.