Review

Mechanical forces direct stem cell behaviour in development and regeneration

  • Nature Reviews Molecular Cell Biology 18, 728742 (2017)
  • doi:10.1038/nrm.2017.108
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Abstract

Stem cells and their local microenvironment, or niche, communicate through mechanical cues to regulate cell fate and cell behaviour and to guide developmental processes. During embryonic development, mechanical forces are involved in patterning and organogenesis. The physical environment of pluripotent stem cells regulates their self-renewal and differentiation. Mechanical and physical cues are also important in adult tissues, where adult stem cells require physical interactions with the extracellular matrix to maintain their potency. In vitro, synthetic models of the stem cell niche can be used to precisely control and manipulate the biophysical and biochemical properties of the stem cell microenvironment and to examine how the mode and magnitude of mechanical cues, such as matrix stiffness or applied forces, direct stem cell differentiation and function. Fundamental insights into the mechanobiology of stem cells also inform the design of artificial niches to support stem cells for regenerative therapies.

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Acknowledgements

The authors thank J. Li for assistance with revising this manuscript and D. Zhang for input on the figures. Funding was provided by the National Institute of Dental and Craniofacial Research of the US National Institutes of Health (NIH) under Award Numbers 5R01DE013033 (D.M.) and K08DE025292 (K.H.V.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Author information

Affiliations

  1. Wyss Institute for Biologically Inspired Engineering and John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA.

    • Kyle H. Vining
    •  & David J. Mooney

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Contributions

K.H.V. and D.J.M. researched data for the article, contributed to discussion of the content, wrote the article and reviewed and/or edited the manuscript before submission.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to David J. Mooney.

Supplementary information

PDF files

  1. 1.

    Supplementary information S1 (table)

    Mechanical cues guide development processes

  2. 2.

    Supplementary information S2 (box)

    Techniques to apply and measure extrinsic forces on cells

  3. 3.

    Supplementary information S3 (table)

    Stem cells respond diversely to forces in models of mechanobiology

Glossary

Cadherin–catenin complexes

Complexes of cellular receptors termed cadherins, which bind to other cells, with β-catenin, an intracellular molecule, that connect to the actin cytoskeleton in epithelial tissues to convey forces between cells.

Dorsal closure

Closure of a dorsal epidermal opening that is initially formed naturally during embryonic development of Drosophila melanogaster; this process has similarities to wound healing in mammals.

Cortical tension

A type of cytoskeletal tension caused by actomyosin-generated forces; it contributes to cell shape and mechanical properties.

RHO-associated protein kinase

(ROCK). A serine/threonine kinase that can regulate actomyosin contractility and is downstream of RHOA and other pathways.

Stomodeum

A frontal opening in the developing embryo that forms a primordial mouth, separated from the pharynx by an oropharyngeal membrane.

Traction forces

Forces on extracellular matrix or other cells generated by receptor binding and actomyosin contractility.

Fractal patterns

Highly branched geometric patterns that are formed from repeated symmetrical branching, often across multiple length scales.

Submandibular salivary gland

One of the major salivary glands, it features a branched ductal structure that opens into the oral cavity, with secretory end pieces called acini that produce saliva by secretion of water, salts, proteins and other macromolecules.

Focal adhesions

Large and dynamic protein complexes of matrix receptors, actin cytoskeleton and other cytoskeletal and signalling molecules that link the cytoskeleton to the extracellular matrix.

Isometric muscle contraction

A type of force generated by muscle while maintaining constant muscle length and joint angle.

Convective flow

Fluid flow that transfers mass and/or heat down a fluid pressure gradient.

Microfluidics

The precise control of fluid shear forces and flow rates in micro-scale geometries, such as micro-channels.

Substrate creep

The deformation, or flow, of a material during a constant application of stress.

Stress stiffening

The mechanical stiffening of a polymer network with increasing strain.

Sarcomere

A fundamental active unit in skeletal muscle that generates force from overlapping striations of actin and myosin.