Introduction

Much like whole organisms, single cells have the ability to “sense” and respond to their surroundings. This “sensing” not only includes monitoring and responding to changes in extracellular chemical messages, but also the physical nature of the cell’s microenvironment, particularly the components of the extracellular matrix (ECM). Anchorage to the surrounding ECM is important for many cellular functions and is mediated primarily by the integrin family, a group of heterodimeric transmembrane proteins that provide physical links of the cell to the external environment. Although integrins were once viewed as structural membrane proteins providing anchor points involved in cell adhesion and movement, they are now known to be centrally important for sensing the external environment and regulating the precise intracellular responses necessary for proper mechanotransduction.

Recent evidence suggests that besides its biochemical composition, the dimensional and rheological properties of the ECM are involved in signaling processes that not only affect cell motility, but also a multitude of intracellular second messenger pathways and gene regulation. In this chapter, we review how cells and their surrounding ECM interact, particularly focusing on integrins and fibronectin, and examine how their points of contact are involved in inside-out and outside-in signaling for setting the stage for mechanotransduction. In addition, a second major focus will be on the most recent findings regarding cellular mechanosensing and its relationship to the ECM. Furthermore, we describe how alterations to matrix components can lead to altered cellular motility, phenotype, and cellular responses.