Collection |

Mechanics of cells and tissues

This collection of recent articles from Nature Research journals focuses on the latest efforts to understand the roles of mechanical forces in animal cells and tissues. It highlights the broad involvement of mechanical forces in different biological contexts, their roles in development, physiology and disease, and discusses how these forces are sensed and transduced to produce biologically-relevant responses. The collection also showcases new technical approaches to study and modulate mechanobiology, which in the future could be used control cell fate and behaviour for therapeutic benefits. This collection is aimed for researchers from a broad range of disciplines — biologists, physicists and theoreticians alike — and we hope that it will foster inter-disciplinary initiatives to study biological systems.

Reviews

Advances in biomaterials have enabled control over desired cell responses. Here, the authors highlight key analytical and bioprocessing techniques, outlining a framework for incorporating these tools into designing functionally optimal biomaterials.

Perspective | | Nature Materials

Coordinated movements of cell collectives are important for morphogenesis, tissue regeneration and cancer cell dissemination. Recent studies, mainly using novel in vitro approaches, have provided new insights into the mechanisms governing this multicellular coordination, highlighting the key role of the mechanosensitivity of adherens junctions and mechanical cell–cell coupling in collective cell behaviours.

Review Article | | Nature Reviews Molecular Cell Biology

Physical cues regulate stem cell fate and function during embryonic development and in adult tissues. The biophysical and biochemical properties of the stem cell microenvironment can be precisely manipulated using synthetic niches, which provide key insights into how mechanical stimuli regulate stem cell function and can be used to maintain and guide stem cells for regenerative therapies.

Review Article | | Nature Reviews Molecular Cell Biology

Mechanical cues from the microenvironment can be efficiently transmitted to the nucleus to engage in the regulation of genome organization and gene expression. Recent technological and theoretical progress sheds new light on the relationships between cell mechanics, nuclear and chromosomal architecture and gene transcription.

Review Article | | Nature Reviews Molecular Cell Biology

Soon after their discovery in 2010, Piezo channels became a paradigm for studying mechanosensitive ion channels. These channels respond to physiologically relevant forces in diverse cellular contexts, and their dysfunction has been linked to various diseases. We are now starting to understand gating mechanisms of Piezo channels and their key roles in physiology.

Review Article | | Nature Reviews Molecular Cell Biology

The transcription factors YAP and TAZ have recently emerged as being conserved transducers of mechanical signals into cells and mediators of processes such as proliferation, migration and cell fate decision. The roles of YAP-mediated and TAZ-mediated mechanotransduction have now been documented in many physiological and pathological contexts, providing novel insights into cellular mechano-responses and their consequences.

Review Article | | Nature Reviews Molecular Cell Biology

As leukocytes travel in the bloodstream, navigate through tissues and mediate effector functions, their behaviour is influenced by mechanical forces. In this Review, Morgan Huse explains how mechanical force regulates receptor activation, cell migration, intracellular signalling and intercellular communication.

Review Article | | Nature Reviews Immunology

The field of active matter studies how internally driven motile components self-organize into large-scale dynamical states and patterns. This Review discusses how active matter concepts are important for understanding cell biology, and how the use of biochemical components enables the creation of new inherently non-equilibrium materials with unique properties that have so far been mostly restricted to living organisms.

Review Article | | Nature Reviews Materials

The actin cytoskeleton of B cells is extensively coupled to B cell receptor (BCR) signalling pathways. This Review summarizes recent evidence that indicates that actin orchestrates BCR signalling at the plasma membrane, and discusses the role of the cytoskeleton in antigen presentation, affinity maturation and the functional specialization of B cells.

Review Article | | Nature Reviews Immunology

Physical forces influence the growth and development of all organisms. In the second Review in the Series on Mechanobiology, Trepat and co-authors describe techniques to measure forces generated by cells, and discuss their use and limitations.

Review Article | | Nature Cell Biology

In this Review, we will discuss how the interplay and feedback between mechanical and biochemical signals control tissue morphogenesis and cell fate specification in embryonic development.

Review Article | | Nature Cell Biology

Primary research

Mesenchymal stem cell (MSC) fate can be mechanically regulated by substrate stiffness but this is difficult to control in a 3D hydrogel. Here the authors identify miRNAs that change expression in response to substrate stiffness and RhoA signalling and show that they can bias MSC fate in a 3D soft hydrogel.

Article | open | | Nature Communications

The cryo-electron microscopy structure of full-length mouse Piezo1 reveals six Piezo repeats, and 26 transmembrane helices per protomer, and shows that a kinked helical beam and anchor domain link the Piezo repeats to the pore and control gating allosterically.

Article | | Nature

In multi-layered epithelia tight junctions (TJ) are confined to the most suprabasal viable layer. Here the authors show that this is regulated by ubiquitously localized E-cadherin tuning junctional tension and EGFR activity to inhibit TJ formation in lower layers while promoting TJ stability in the granular layer 2.

Article | open | | Nature Communications

Adenomatous polyposis coli (APC) regulates the localization of some mRNAs at cellular protrusions but the underlying mechanisms and functional roles are not known. Here the authors show that APC-dependent RNAs are enriched in contractile protrusions, via detyrosinated microtubules, and enhance cell migration.

Article | open | | Nature Communications

Cells in the connective tissue are surrounded by a heterogeneous network of biopolymers. Here, the authors investigate how such heterogeneity affects cellular mechanosensing by simulating the deformation response of experimental and modelled biopolymer networks to locally applied forces.

Article | open | | Nature Communications

Single-particle electron cryo-microscopy analysis of the mechanotransduction channel NOMPC reveals that it contains a bundle of four helical spring-shaped ankyrin repeat domains that undergo motion, potentially allowing mechanical movement of the cytoskeleton to be coupled to the opening of the channel.

Letter | | Nature

Cortical tension is thought to be generated by myosin II, and little is known about the role of actin network properties. Chugh et al. demonstrate that actin cortex thickness, determined by actin filament length, influences cortical tension.

Article | | Nature Cell Biology

The transcriptional co-activator YAP is known to operate downstream of mechanical signals arising from the cell niche. Here the authors demonstrate that YAP controls cell mechanics, force development and adhesion strength by promoting the transcription of genes related to focal adhesions.

Article | open | | Nature Communications

Epidermal growth factor receptor and its isoform HER2 are recruited to nascent cellular adhesion sites and play an important role in the rigidity sensing of cells on stiff substrates, this activity being dependent on Src-mediated phosphorylation.

Article | | Nature Materials

Zebrafish neuroectoderm morphogenesis is influenced by the mesoderm germ layer. Smutny et al. now show that friction forces between cells moving in opposite directions, mediated by E-cadherin adhesion, determine the position of the neural anlage.

Article | | Nature Cell Biology

Technical articles and Protocols

Purely elastic biomimetic soft materials are used to characterize the mechanical response of cells, but do not resemble real tissues. Here the authors develop a viscoelastic solid hydrogel, based on polyacrylamide, that can be tuned to closely resemble soft tissue, and show the influence of viscous dissipation on cellular mechanical sensing.

Article | open | | Nature Communications

Molecular force microscopy employs a combination of fluorescence polarization microscopy and molecular tension sensors to determine the orientation of cellular forces. The technology is demonstrated for integrin-mediated forces in platelets and fibroblasts.

Brief Communication | | Nature Methods

Cellular mechanical forces are regulated by Rho GTPases. Here the authors develop an optogenetic system to control the spatiotemporal activity of RhoA, and show that directing a RhoA activator to the plasma membrane causes contraction and YAP nuclear localization, whereas directing it to the mitochondria causes relaxation.

Article | open | | Nature Communications