Every adherent cell exerts contractile forces-called tractions-on its substrate. These forces can now be visualized on the submicron scale through the implementation of one of a variety of technologies collectively known as traction microscopy (TM). We provide here a historical review of TM and focus on its application to mechano-sensing of the adherent cell, i.e., how the adherent cell senses and responds to mechanical properties of its microenvironment. 4.1 IntroductionMajor advances in cell biology rely in large part on advances in imaging technologies. As an example, consider the now burgeoning
field of mechanobiology. Despite the widely held view that the single cell is a force-bearing member capable of both generating and responding to physical force, underlying forces were entirely invisible to observation. These hidden forces can now be visualized through the force imaging technology called TM. Using TM, forces have been implicated in cellular functions as diverse as migration, spreading, differentiation, and growth, and diseases as profound as asthma, acute lung injury, and cancer [1-13].In this chapter, we will provide a historical review of TM with an emphasis on key technological advances. We will bring these advances to bear upon the topic of mechanosensing in the adherent cell, i.e., how the cell senses and responds to physical properties of its microenvironment. By physical properties, we refer to stiffness, thickness, mechanical stretch, and fluid flow, as well as mechanical interactions among neighboring cells. The roles of specific biological features such as soluble factors, biochemical constituents of the extracellular matrix, and downstream effectors of cell signaling have been elegantly described elsewhere [14-26]. Here we will focus specifically on the tractions themselves and describe their spatio-temporal regulation and evolution in the cell through the newly discovered physical principles of fluidization, plithotaxis, and kenotaxis. 4.2 What Are Tractions?