Physical forces of gravity, hemodynamic stresses, and movement play a critical role in tissue development. Yet, little is known about how cells convert these mechanical signals into a chemical response. This review attempts to place the potential molecular mediators of mechanotransduction (e.g. stretch-sensitive ion channels, signaling molecules, cytoskeleton, integrins) within the context of the structural complexity of living cells. The model presented relies on recent experimental findings, which suggests that cells use tensegrity architecture for their organization. Tensegrity predicts that cells are hard-wired to respond immediately to mechanical stresses transmitted over cell surface receptors that physically couple the cytoskeleton to extracellular matrix (e.g. integrins) or to other cells (cadherins, selectins, CAMs). Many signal transducing molecules that are activated by cell binding to growth factors and extracellular matrix associate with cytoskeletal scaffolds within focal adhesion complexes. Mechanical signals, therefore, may be integrated with other environmental signals and transduced into a biochemical response through force-dependent changes in scaffold geometry or molecular mechanics. Tensegrity also provides a mechanism to focus mechanical energy on molecular transducers and to orchestrate and tune the cellular response.