Schematic illustration of the "mechanical nature" of cellular mechanotransduction mechanisms. Mechanical forces (MF) can induce mechanotransduction by directly altering conformation of an extracellular matrix (ECM) protein and integrin configuration and transmitting forces to the cytoskeleton and nucleus, thus eventually affecting transcription and translation. Also, mechanical forces can unfold a domain of the extracellular protein (M) and expose a cryptic site that may serve as an activating ligand for a cell surface receptor, resulting in a series of signaling events. Also, when mechanical forces are applied to "force receptors" (FR), such as integrins and G proteins, they initiate signal transduction, resulting in transcription followed by translation. As a result, soluble factors are secreted into the ECM, which act on the receptor (R) and then initiate a cascade of signaling events. Note that double arrows indicate intracellular tensions in the actin filaments. (Modified with permission from Wang and Thampatty, Fig. four in Encyclopedia of Biomaterials and Biomedical Engineering, 2008, p.1783-1793, Taylor & Francis).