Review Article | Published:

Material approaches to active tissue mechanics

Abstract

Communities of epithelial cells communicate through intercellular interactions, allowing them to coordinate their motility, which plays a key role in homeostasis, morphogenesis and cancer metastasis. Each cell in the epithelium is a constitutive energy-consuming agent, which can generate forces and interact with other cells through cell–cell junctions. Forces applied through external stimuli or endogenous cellular events are balanced by the cells within the epithelium, resulting in the adjustment of internal tissue contractile stresses and tissue reorganization. Materials science and microengineering techniques can be combined to create controllable environments to study epithelial movement and mechanics. By modulating the cell–material interface and by applying principles of active matter, key aspects of epithelial dynamics and mechanosensing mechanisms can be investigated. In this Review, we discuss epithelial tissues as active materials with particular rheological properties and active behaviours at different length scales. We highlight 2D and 3D materials for the study of epithelial dynamics and summarize key methods for the probing of epithelial mechanics. Tissue responses to mechanical stimuli are examined from the molecular level to the tissue level, and the effects of the shape, architecture and stiffness of the microenvironment are discussed.

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Acknowledgements

The authors thank group members from Mechanobiology Institute (MBI), Singapore, and Institut Jacques Monod (IJM), Paris, for helpful discussions. The authors thank R.M. Mège from IJM for help improving Fig. 1 and the text in the “Cell signalling and mechanical forces” section. W.X. received funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007–2013) under REA grant agreement no. PCOFUND-GA-2013-609102, through the PRESTIGE programme coordinated by Campus France. Financial support from the European Research Council under the European Union’s Seventh Framework Program (FP7/2007–2013)/ERC grant agreement no. 617233 (B.L.), Agence Nationale de la Recherche (ANR) “POLCAM” (ANR-17-CE13-0013), The Groupama Foundation — Research for Rare Diseases (D.D.), NUS-USPC programme, The LABEX “Who am I?” and MBI, Singapore, is gratefully acknowledged. C.T.L. and D.D. recognize support from the Human Frontier Science Program (RGP0038/2018). T.B.S. acknowledges support from the Lee Kuan Yew (LKY) Postdoctoral fellowship and Tier 1 grant from the Ministry of Education (MOE), Singapore.

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W.X., T.B.S., C.T.L. and B.L. conceived of the manuscript; W.X., T.B.S. and B.L. wrote the manuscript; W.X., T.B.S. and B.L. designed the figures; all authors edited the manuscript.

Correspondence to Wang Xi or Chwee Teck Lim or Benoit Ladoux.

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Further reading

Fig. 1: Mechanosensitive molecular networks and signalling.
Fig. 2: Theoretical modelling.
Fig. 3: Epithelial tissue as active matter.
Fig. 4: Cell responses to substrate stiffness.
Fig. 5: Cell responses to 2D and 3D environments.
Fig. 6: Cell responses to out-of-plane structures.