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Appreciating force and shape — the rise of mechanotransduction in cell biology

Abstract

Although the shapes of organisms are encoded in their genome, the developmental processes that lead to the final form of vertebrates involve a constant feedback between dynamic mechanical forces, and cell growth and motility. Mechanobiology has emerged as a discipline dedicated to the study of the effects of mechanical forces and geometry on cell growth and motility — for example, during cell–matrix adhesion development — through the signalling process of mechanotransduction.

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Figure 1: Mechanotransduction.
Figure 2: Timeline of milestones in the history of mechanotransduction research.
Figure 3: Experimental tools in mechanobiology.

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Acknowledgements

T.I. was supported by a Postdoctoral Fellowship from the American Heart Association. H.W. was supported by a Marie Curie International Outgoing Fellowship within the Seventh European Commission Framework Programme (PIOF-GA-2012-332045). M.P.S. was partially supported by the Mechanobiology Institute, National University of Singapore.

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Correspondence to Michael P. Sheetz.

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PowerPoint slides

Glossary

Actomyosin

A basic force-producing or structural unit in cells consisting of myosin motors that bind and pull on actin filaments.

Adhesome

The combined molecular composition of focal adhesions.

Dorsal stress fibres

Long parallel actomyosin bundles that are anchored to focal adhesions at one end.

Finite element analysis

A numerical method of approximation.

Frank–Starling mechanism

Also known as the Frank–Starling law of the heart; states that there is a direct relationship between the force of cardiac contraction and the volume of blood filling the heart. The stretching of muscle fibres through the increasing blood volume increases calcium sensitivity, thus causing the formation of more actin–myosin crossbridges and hence more force.

Isotropic spreading

Spreading of cells during which their entire edge (or large parts of it) extends rapidly.

Ligand valency

The combined effects of the binding of multiple ligands.

Local contraction units

Multiprotein complexes that are similar to muscle sarcomeres and are used by cells to measure substrate rigidity.

Microcontact printing

Also known as micropatterning. A form of surface patterning, usually with fluorescent-labelled extracellular matrix proteins.

Optical trap

Also known as laser tweezers. An appliance that provides force from a highly focused laser beam to hold or move objects such as microspheres.

Sliding filament theory

A model of muscle contraction postulating that thin filament (mostly actin)-containing I-bands slide past the myosin-containing A-bands to generate force.

Swinging crossbridge model

The first model of the myosin power stroke, which suggests that ATP-dependent changes in the actin–myosin crossbridge angle would cause the thin filaments to slide past the myosin (see sliding filament theory).

Transverse arcs

Curved, antiparallel actomyosin bundles that interact with dorsal stress fibres and flow inward towards the cell centre.

Ventral stress fibres

Antiparallel actomyosin bundles anchored to focal adhesions at both ends.

Z-disc

A protein complex that defines the boundaries of the muscle sarcomere. It anchors and links actin filaments and titin from adjacent sarcomeres, provides mechanical stability and is a centre of cardiomyocyte signal transduction, including mechanotransduction.

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Iskratsch, T., Wolfenson, H. & Sheetz, M. Appreciating force and shape — the rise of mechanotransduction in cell biology. Nat Rev Mol Cell Biol 15, 825–833 (2014). https://doi.org/10.1038/nrm3903

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