Introduction

Mechanical forces can act as insoluble cues that affect cellular events such as migration, differentiation, growth, and apoptosis. The response to mechanical stimuli leads to adaptive and functional changes in tissue that contribute to physiological homeostasis (Hughes-Fulford 2004; Ingber 2006). Since many diseases occur in a setting where cells are exposed to abnormal forces, it is now evident that alterations in the mechanical context of healthy tissue contributes to pathological responses, such as in hypertension, asthma, and cancer (Ingber 2003; Huang and Ingber 2005). Mechanical forces that affect cellular responses also arise from within cells. Cells generate traction forces through myosin motors and cytoskeletal filaments that are essential for their locomotion and contraction (Lauffenburger and Horwitz 1996; Ridley et al. 2003). These traction forces appear to regulate the same cellular events that are observed with external forces, suggesting a common mechanism for transducing forces into biochemical responses (Chen et al. 2004). For these reasons, identifying the underlying principles in mechanotransduction has been an active area of research.

Depending on the tissue system, cells experience different kinds of external forces. Impulsive forces occur in the musculoskeletal system where strains of 3000–4000 με are common in bone and forces up to 9 kN have been reported in tendons during physical exertion (Lanyon and Smith 1969; Wang 2006). Rhythmic mechanical forces are pervasive in the normal physiology of the vascular or pulmonary systems. Cardiac or ventilatory cycles produce a combination of shear, tensile, and compressive stresses as blood or air flows across the cell surface and pressure levels rise and fall (Davies 1995; Waters et al. 2002). These forces act locally at the site of force but are also dispersed through viscoelastic tissues. These forces propagate along a network of macromolecules that composes the extracellular matrix (ECM), which surrounds the cells, as well as through cell–cell contacts that link adjacent cells. Because these forces are distributed throughout the tissue, the magnitudes of forces acting at the cellular level are not as large as their tissue-level counterparts and range from pico- to nano-Newtons. Yet, even these small forces are able to elicit mechanotransductive responses from cells. Normal physiological processes expose cells to a variety of mechanical stimuli that differ in magnitude, frequency, and direction, but how cells sense and respond to forces at the molecular level to produce orchestrated responses is currently under investigation.