Measuring Patterns, Regulation, and Biologic Consequences of Cellular Traction Forces

The exchange of mechanical signals between mammalian cells and their extracellular matrix microenvironments is a focus of keen interest for biologists in the diverse fields of development, vascular disease, tissue engineering, and oncology. The molecular machinery of cellular mechanical signal response includes at least three major components: transmembrane adhesion receptors for extracellular matrix; the microfilament and microtubule cytoskeletal systems; and the Rho family of GTP-binding proteins that modulate the density and contraction state of cytoskeletal elements. Complex signaling pathways link these three arms of mechanical signal response as they interact with the extracellular matrix microenvironment. Arrays of microfabricated silicon posts have provided a system for reporting the traction force at individual cell-matrix interaction sites. Volumetric imaging of posts with known spring constants allows the efficient analysis of maps of cell traction force vectors and their coincidence with both actin polymerization and signal molecule localization. The effects of cytoskeletal contraction on patterns of cell traction forces are reported here. We have also defined unique patterns of force generation that are specific for cells of fibroblast, endothelial, epithelial, and smooth muscle lineages. Cell-generated mechanical forces directly affect patterning of the matrix milieu and the mechanical cues that are stored in it. The contributions of signaling molecules including non-receptor tyrosine kinases and GTPases to the exchange of mechanical data between the cell and its environment are discussed. These investigations have important implications for understanding and optimizing cellular growth behaviors during tissue development and repair in normal and microgravity settings.