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Forcing cells into shape: the mechanics of actomyosin contractility

Key Points

  • The capability of cells to generate contractile forces originates from the activity of the molecular motor myosin II on its substrate actin filaments.

  • Although the molecular constituents of contractility are well conserved across cell types, the organization of myosin and actin filaments varies widely from highly organized sarcomeres in striated muscle to non-sarcomeric organizations in smooth and non-muscle cells.

  • In sarcomeres, actomyosin geometry regulates force transmission and is well understood. The non-sarcomeric organiazations of actomyosin require novel mechanisms of force transmission, from molecular to cellular length scales, and alternative mechanisms of contractility.

  • Alternativee mechanisms of force transmission invoke nonlinear response of actin filaments and spatial localization of actin filament assembly.

  • Non-sarcomeric actomyosin assemblies facilitate large shape changes, and mechanochemical feedback exists to coordinate assembly dynamics with contractility.

  • Actomyosin networks are also used in cell mechanosensing and facilitate a novel mode of intracellular transport.

Abstract

Actomyosin-mediated contractility is a highly conserved mechanism for generating mechanical stress in animal cells and underlies muscle contraction, cell migration, cell division and tissue morphogenesis. Whereas actomyosin-mediated contractility in striated muscle is well understood, the regulation of such contractility in non-muscle and smooth muscle cells is less certain. Our increased understanding of the mechanics of actomyosin arrays that lack sarcomeric organization has revealed novel modes of regulation and force transmission. This work also provides an example of how diverse mechanical behaviours at cellular scales can arise from common molecular components, underscoring the need for experiments and theories to bridge the molecular to cellular length scales.

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Figure 1: Types of contractile deformations generated by cells and tissues.
Figure 2: Contractility in sarcomeres.
Figure 3: Contractility in disordered actomyosin bundles.
Figure 4: Inherent contractility of adherent cells.

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Acknowledgements

The authors thank Y. Beckham and B. Hissa for contributing images for Figure 1. M.L.G. is supported by the Packard Foundation, an American Asthma Foundation grant and NSF-MCB 1344203. M.M. is supported by NSF-CMMI 1434095. M.L.'s group belongs to the CNRS consortium CellTiss. M.L. was supported by grants from Université Paris-Sud and CNRS, Marie Curie Integration Grant PCIG12-GA-2012-334053 and “Investissements d'Avenir” LabEx PALM (ANR-10-LABX-0039-PALM). M.L. and M.L.G. were supported by the University of Chicago FACCTS programme. This work was supported by the University of Chicago MRSEC (NSF-DMR 1420709).

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PowerPoint slides

Glossary

Isotropic contraction

Shortening that is uniform in all directions.

Anisotropic stresses

Shortening that is not uniform in all directions.

Z-line

A region at the boundaries of muscle sarcomeres in which the actin filaments are anchored. It appears as a dark transverse line in electron micrographs.

Force–velocity curve

The relationship between the force applied to a motor and the speed at which it moves relative to its substrate.

Myofibril

The structural unit of striated muscle fibres, which is formed from longitudinally joined sarcomeres. Several myofibrils form each fibre.

Unloaded velocity

The speed at which a motor moves under no applied load. Typical unloaded velocities for myosin II motors range from 50–1,000 nm s−1.

Stall force

The applied force that stops the motion of the motor. Typical stall forces for individual molecular motors are 1–10 pN.

Lamella

RHOA-dependent actomyosin organelles in adherent cells. Actomyosin is organized into a variety of contractile bundles and networks and tethered to the matrix by mature focal adhesions.

Transverse arcs

Actomyosin bundles in the lamella that are parallel to the cell periphery and undergo myosin II-dependent retrograde flow towards the cell centre.

Radial stress fibres

Actin bundles tethered at one end to focal adhesions and integrated into transverse arcs along their length and, thus, oriented in a radial fashion with respect to the cell centre on the dorsal surface. Radial stress fibres do not contain myosin II and assemble in a DIA1- and INF2-dependent manner. They are also known as dorsal stress fibres.

Peripheral bundles

Actomyosin bundles found at non-adherent edges of cells that are responsible for cell shape maintenance.

Ventral stress fibres

Actomyosin bundles formed at the ventral surface that are attached to focal adhesions at each end.

Contractile strain

Deformation of a structure that results in shortening of length, area or volume.

Steady-state flow

Movements that occur at a constant rate, or velocity, over time.

Stress relaxation

The decrease of force that occurs in structures owing to viscous, or fluid, effects.

Compressive forces

Force that results in pushing, or compression, on a structure.

Tensile force

Force that results in pulling, or tension, on a structure

Compliance

The tendency of a material to deform in response to an external force. A more compliant material will deform to a greater extent than a less compliant one.

Focal adhesions

Cellular structures that link the extracellular matrix on the outside of the cell, through integrin receptors, to the actin cytoskeleton inside the cell.

Adherens junctions

Protein complexes that contain cadherin and catenin proteins. They are formed between neighbouring cells in the tissue and serve not only to maintain cell–cell adhesion but also to regulate intracellular signalling and cytoskeletal organization.

Elastic response

The tendency of structures to store mechanical energy. The initial shape is preserved upon release of external forces.

Traction force microscopy

A technique to calculate stresses generated by cells by measuring the deformation of the matrix to which they are attached.

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Murrell, M., Oakes, P., Lenz, M. et al. Forcing cells into shape: the mechanics of actomyosin contractility. Nat Rev Mol Cell Biol 16, 486–498 (2015). https://doi.org/10.1038/nrm4012

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