Cells sense their physical three-dimensional environment — properties of the extracellular matrix, neighbouring cells and physical stress — by translating mechanical forces and deformations into biochemical signals. In turn, these signals can adjust cellular and extracellular structure. This mechanosensitive feedback modulates cellular functions as diverse as proliferation, differentiation, migration and apoptosis, and is crucial for organ development and homeostasis. Any molecular defect that interrupts or alters this chain of mechanical sensing and subsequent cell signalling events could perturb the normal cellular function and potentially lead to diverse diseases such as loss of hearing, cardiovascular disease, muscular dystrophy and cancer.
This special Focus reflects our current understanding of mechanotransduction — from how cells sense mechanical forces in different tissues to how these mechanical forces are transduced into biochemical signals — in development, normal physiology and disease.
From the editors
doi:10.1038/nrm2613
Nature Reviews Molecular Cell Biology 10, 1 (2009)
Research Highlights
Mechanotransduction: Under tension
Ekat Kritikou
doi:10.1038/nrm2606
Nature Reviews Molecular Cell Biology 10, 3 (2009)
Mechanotransduction: Bent out of shape
Ekat Kritikou
doi:10.1038/nrm2605
Nature Reviews Molecular Cell Biology 10, 6-7 (2009)
Reviews
Balancing forces: architectural control of mechanotransduction
Christopher C. DuFort, Matthew J. Paszek & Valerie M. Weaver
doi:10.1038/nrm3112
Nature Reviews Molecular Cell Biology 12, 308-319 (2011)
Cells exist within a three-dimensional microenvironment in which they are exposed to mechanical and physical cues. Disrupting these cues compromises tensional homeostasis, which suggests that there is complex interplay between the extracellular microenvironment and cellular function. As alterations in the extracellular matrix can sustain perturbed tensional homeostasis, it serves as a mechanically based memory-storage device.
Environmental sensing through focal adhesions
Benjamin Geiger, Joachim P. Spatz & Alexander D. Bershadsky
doi:10.1038/nrm2593
Nature Reviews Molecular Cell Biology 10, 21-33 (2009)
Cells respond to a wide range of signals from the surrounding extracellular matrix. Research into the complex interplay between cell adhesion and the cytoskeleton, combined with advanced surface nanoengineering technologies, can shed light on the mechanisms by which cells sense the neighbouring nanoenvironment.
Mechanotransduction in development: a growing role for contractility
Michele A. Wozniak & Christopher S. Chen
doi:10.1038/nrm2592
Nature Reviews Molecular Cell Biology 10, 34-43 (2009)
Mechanical forces regulate basic cellular processes, such as proliferation, differentiation and tissue organization during embryogenesis. What are the mechanisms that underlie force-induced mechanotransduction during development? And what is the role of actomyosin-mediated contractile forces in the regulation of cell and tissue structure and function?
Neurosensory mechanotransduction
Martin Chalfie
doi:10.1038/nrm2595
Nature Reviews Molecular Cell Biology 10, 44-52 (2009)
Neurons that sense touch, sound and acceleration respond rapidly to specific mechanical signals. But what are the proteins that transduce these signals? Current studies are directed towards characterizing channel proteins as candidate transduction molecules and determining how they are mechanically gated.
Mechanotransduction in vascular physiology and atherogenesis
Cornelia Hahn & Martin A. Schwartz
doi:10.1038/nrm2596
Nature Reviews Molecular Cell Biology 10, 53-62 (2009)
Blood flow is crucial for vascular morphogenesis and physiology. Endothelial cells respond to blood flow by transducing mechanical forces into biochemical signals that regulate cellular responses. Chronic exposure to disturbed flow causes the constant activation of these cellular responses, which cause vessel dysfunction and disease.
Mechanotransduction gone awry
Diana E. Jaalouk & Jan Lammerding
doi:10.1038/nrm2597
Nature Reviews Molecular Cell Biology 10, 63-73 (2009)
Cells sense their physical surroundings by translating mechanical forces and deformations into biochemical signals. Defects in mechanotransduction are implicated in the development of many diseases, ranging from muscular dystrophies, cardiomyopathies and loss of hearing to cancer progression and metastasis.
Perspective
Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus
Ning Wang, Jessica D. Tytell & Donald E. Ingber
doi:10.1038/nrm2594
Nature Reviews Molecular Cell Biology 10, 75-82 (2009)
Mechanical forces that are exerted on surface-adhesion receptors can be channelled along cytoskeletal filaments and concentrated at distant sites in the cytoplasm and nucleus. How do these forces act at a distance to induce mechanochemical conversion in the nucleus, and what effects can they have on the cell?
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