We all have our own way of dealing with stress, but how do our cells deal with it at a molecular level? Cells sense physical stress from their three-dimensional environment — certain properties of the extracellular matrix, neighbouring cells and other mechanical forces. Extensive research has uncovered how mechanical forces are transduced into biochemical signals (mechanotransduction) and how mechanotransduction affects cellular function. Several molecules that are involved in mechanotransduction, including ion channels, cell adhesion receptors, cytoskeletal and extracellular matrix molecules, have recently been identified. Progress has also been made towards measuring and defining in vivo forces, and understanding their roles in pathogenesis. Any molecular defect that interrupts or alters mechanical sensing and subsequent cell signalling events could perturb the normal cellular function and potentially lead to various diseases.

This month's Focus (http://www.nature.com/nrm/focus/mechanotransduction) considers different aspects of mechanotransduction — from how cells sense mechanical forces through adhesion molecules (Geiger, Spatz and Bershadsky, page 21) and through ion channels (Chalfie, page 44), to mechanochemical coupling between the cell surface and the nucleus, as Ingber, Wang and Tytell explain on page 75. Understanding how cells sense and respond to mechanical cues is important not only for our understanding of embryogenesis (Wozniak and Chen, page 34) and vascular physiology (Hahn and Schwartz, page 53), but also for diseases, ranging from muscular dystrophies and cardiomyopathies to cancer progression and metastasis (Jaalouk and Lammerding, page 63).

We wish all our readers, authors and referees a happy and productive New Year!