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

Mechanical forces are important regulators of cell function and behaviour. This role is partly achieved through the modulation of cell metabolism, which, reciprocally, affects tissue mechanics. Unravelling the mechanisms of this crosstalk will increase our understanding of how cells interact with their microenvironment.

Review Article | | Nature Reviews Molecular Cell Biology

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 novelin vitroapproaches, 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

Integrin extracellular matrix receptors establish contacts between the cell interior and the cell microenvironment. Integrins are subjected to complex biochemical and mechanical regulation, which allows cells to respond to extracellular matrix with different physicochemical properties and fine-tunes cell behaviour.

Review Article | | Nature Reviews Molecular Cell Biology

Primary research

The effect of mechanical cues on the behaviour of cells in culture is well documented, but such effects are more difficult to study in vivo. Norbert Perrimon and colleagues find that stem cells of the Drosophila gut sense mechanical signals in vivo through the stretch-activated ion channel Piezo. Piezo is expressed in a subset of enteroendocrine precursor cells. Loss of Piezo reduces the differentiation of the enteroendocrine lineage in adults, while the over expression of this gene in gut stem cells has the reverse effect. Further analysis shows that Piezo activates the calcium signalling pathway in response to mechanical stimuli.

Letter | | Nature

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 Access | | Nature Communications

Mechanosensitive cation channels convert external mechanical stimuli into various biological actions, including touch, hearing, balance and cardiovascular regulation. The eukaryotic Piezo proteins are mechanotransduction channels, although their structure and gating mechanisms are not well elucidated. In related papers in this issue of Nature, two groups report cryo-electron microscopy structures of the full-length mouse Piezo1 and reveal three flexible propeller blades. Each blade is made up of at least 26 helices, forming a series of helical bundles, which adopt a curved transmembrane region. A kinked beam and anchor domain link these Piezo repeats to the pore, giving clues as to how the channel responds to membrane tension and mechanical force.

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 Access | | 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 Access | | 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 Access | | Nature Communications

Mechanosensation forms the basis of many of our senses, including touch, balance, hearing and pain. Mechanically gated ion channels are responsible for transmitting mechanical force into electrical signals. However, how this occurs is not well understood at the molecular level. Here the authors report the structure of the Drosophila mechanotransduction channel NOMPC by single-particle cryo-electron microscopy. The channel contains a long, helical domain of ankyrin repeats, which appears to undergo a spring-like motion. This motion allows the mechanical movement of the cytoskeleton to be relayed into opening 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 Access | | 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

Cytokinesis, which physically separates the dividing cells at the end of epithelial cell division, involves the remodelling of adhesive junctions between the dividing cell and its neighbours. This process depends on the cytoskeletal protein myosin II (MyoII) in the non-dividing neighbouring cells. Yohanns Bellaïche and team investigated how cytokinesis in the dividing cell is coordinated with MyoII activity in its neighbours in living fly tissue and find that mechanical communication is the answer. Specifically, the cytokinetic ring pulls at local adherens junctions causing their elongation, which results in decreased levels of E-cadherin protein at these sites. This is sensed by the contracting neighbouring cells, which then promote actomyosin flows and MyoII accumulation at the base of the ingressing junctions. The authors propose that this mechano-sensing mechanism drives remodelling of adherens junction and highlight the role of actomyosin flows in epithelial cell dynamics.

Letter | | Nature

Epithelial cell layers serve as barriers for the organs they cover, yet they continuously undergo cell division and cell death. So how do these dynamic processes avoid compromising the barrier function of epithelia? Jody Rosenblatt and colleagues previously reported in Nature that when epithelial cells become too crowded they trigger the stretch-activated channel Piezo1 to effect extrusion of cells that later die. They now ask how epithelia deal with the opposite situation—cell death. It emerges that, following cell death, the low density of surrounding cells also activate Piezo1, driving cell division to rebalance the cell numbers. The authors provide insights into the molecular mechanism through which stretch triggers cell division, and propose that whether Piezo1 signals for cell division or cell extrusion depends on the type of mechanical forces that it experiences.

Letter | | Nature

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 Access | | 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 Access | | Nature Communications