Review

Mechanobiology of collective cell behaviours

Published online:

Abstract

The way in which cells coordinate their behaviours during various biological processes, including morphogenesis, cancer progression and tissue remodelling, largely depends on the mechanical properties of the external environment. In contrast to single cells, collective cell behaviours rely on the cellular interactions not only with the surrounding extracellular matrix but also with neighbouring cells. Collective dynamics is not simply the result of many individually moving blocks. Instead, cells coordinate their movements by actively interacting with each other. These mechanisms are governed by mechanosensitive adhesion complexes at the cell–substrate interface and cell–cell junctions, which respond to but also further transmit physical signals. The mechanosensitivity and mechanotransduction at adhesion complexes are important for regulating tissue cohesiveness and thus are important for collective cell behaviours. Recent studies have shown that the physical properties of the cellular environment, which include matrix stiffness, topography, geometry and the application of external forces, can alter collective cell behaviours, tissue organization and cell-generated forces. On the basis of these findings, we can now start building our understanding of the mechanobiology of collective cell movements that span over multiple length scales from the molecular to the tissue level.

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Acknowledgements

The authors thank all members of the Institut Jacques Monod (IJM) and Mechanobiology Institute (MBI) teams and T. Chen, D. Delacour, P. Marcq, T. B. Saw and R. Voituriez for helpful discussions and/or critical reading of the manuscript. The authors also thank D. Pitta de Araujo, C. X. Wong and S. Wolf from MBI Science Communication Core for their substantial help with the illustrations. The authors receive financial support from the National University of Singapore/Université Sorbonne Paris Cité (NUS/USPC) and Le Projet International de Coopération Scientifique (PICS) Centre National de la Recherche Scientifique (CNRS) programmes, the European Research Council under the European Union's Seventh Framework Program (FP7/2007–2013)/European Research Council (ERC) (grant agreement number 617233), the LABEX 'Who am I?' and the Mechanobiology Institute (Singapore).

Author information

Affiliations

  1. Institut Jacques Monod (IJM), Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 7592 and Université Paris Diderot, Paris 72505, France.

    • Benoit Ladoux
    •  & René-Marc Mège
  2. Mechanobiology Institute, National University of Singapore, 5A Engineering Drive 1, Singapore 117411.

    • Benoit Ladoux

Authors

  1. Search for Benoit Ladoux in:

  2. Search for René-Marc Mège in:

Contributions

The authors contributed equally to all aspects of the article (researching data for the article, substantial contribution to discussion of content and writing, review and editing of manuscript before submission).

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Benoit Ladoux or René-Marc Mège.

Supplementary information

PDF files

  1. 1.

    Supplementary information S1 (box)

    Examples of morphogenetic processes involving collective cell migration in vivo

  2. 2.

    Supplementary information S2 (box)

    Physical models for collective cell behaviours.

  3. 3.

    Supplementary information S3 (box)

    Mechanocoupling by tight junctions.

  4. 4.

    Supplementary information S4 (box)

    Mechanocoupling by desmosomes and intermediary filaments.

Glossary

Border cells

In Drosophila melanogaster, a cluster of six to eight migratory cells migrating in the egg chamber from the follicular epithelium towards the oocyte.

Lateral line

A system of sense organs found in fish, allowing the detection of movement, vibration and pressure gradients in the water.

Traction forces

Forces exerted by cells on their underlying surfaces during adhesion or migration.

Velocity fields

Maps of the flows of tissues by measuring the displacement field of natural tracers inside the tissues between successive images.

Reynolds number

Dimensionless quantity used in hydrodynamics that represent the ratio between inertial forces and viscous forces. Laminar flows occur at low Reynolds number, whereas turbulent flows appear at high Reynolds number.

Cell extrusion

An expulsion of apoptotic, non-apoptotic or transformed cells from a cell monolayer (apically or basally).

Cryptic lamellipodia

Short lamellipodia forming under neighbouring cells in a migrating monolayer.

Neural crest cells

In vertebrates, a group of migrating cells that arises from the border between the neural plate and the non-neural ectoderm.

Confluence

In cell culture, the state in which 100% of the surface is covered by cells; also called 100% confluence.

Cortical tension

The force per unit length exerted on a part of the cortex, which is a thin layer mainly composed of actin-based proteins and myosin attached to the cell membrane, by the network around it.

Focal adhesions

Integrin-mediated adhesion structures formed at the cell–ECM interface, at the anchorage points of stress fibres.

Optical tweezers

Highly focused laser beams that attract small objects to the centre of the beam.

Stress

The force per unit area.

Strain

A measure of deformation representing the length change in a body relative to a reference length.

Shear

Local stresses exerted tangentially to a defined surface.

Normal stress

Forces perpendicular to a defined surface, such as a cell–cell interface.

Catch bond

A noncovalent bond that shows an increased lifetime with increasing amounts of tensile force applied to the bond.

Förster resonance energy transfer

(FRET). When applied to optical microscopy, a method allowing the determination of the distance (or dynamic changes in the proximity) between two fluorescent molecules within several nanometres.

Cancer-associated fibroblasts

(CAFs). Stromal fibroblasts closely associated with primary tumour cells and participating in the neoplastic process.

Hippo pathway

Also known as the Salvador–Warts–Hippo pathway, this pathway controls organ size in animals through the regulation of cell proliferation and apoptosis.

ERM family

A protein family that is named for three closely related proteins: ezrin, radixin and moesin.

BAR domain

A highly conserved protein dimerization domain that occurs in many proteins involved in cellular membrane dynamics. The BAR domain is banana-shaped, binds to membranes and is capable of sensing membrane curvature by binding preferentially to curved membranes.