Mechanobiology in harness - p531

doi:10.1038/nmat4008

Understanding how cells sense and adapt to their environment, and engineering defined culture substrates, will be central to progress in tissue engineering and regenerative medicine.

Full text - Mechanobiology in harness | PDF (803 KB) - Mechanobiology in harness

Combining insoluble and soluble factors to steer stem cell fate - pp532–537

P. C. Dave P. Dingal and Dennis E. Discher

doi:10.1038/nmat3997

Materials-based control of stem cell fate is beginning to be rigorously combined with traditional soluble-factor approaches to better understand the cells' behaviour and maximize their potential for therapy.

Full text - Combining insoluble and soluble factors to steer stem cell fate | PDF (1,424 KB) - Combining insoluble and soluble factors to steer stem cell fate

Cellular mechanotransduction: Sensing rigidity - pp539–540

José R. García and Andrés J. García

doi:10.1038/nmat3996

Cells use differences in the binding rates between the extracellular matrix and integrin adhesion receptors to sense matrix rigidity.

Full text - Cellular mechanotransduction: Sensing rigidity | PDF (659 KB) - Cellular mechanotransduction: Sensing rigidity

See also: Article by Elosegui-Artola et al.

Stem cell mechanics: Auxetic nuclei - pp540–542

Ning Wang

doi:10.1038/nmat3987

The nuclei of naive mouse embryonic stem cells that are transitioning towards differentiation expand when the cells are stretched and contract when they are compressed. What drives this auxetic phenotype is, however, unclear.

Full text - Stem cell mechanics: Auxetic nuclei | PDF (653 KB) - Stem cell mechanics: Auxetic nuclei

See also: Article by Pagliara et al.

Stem cell differentiation: Sticky mechanical memory - pp542–543

Jeroen Eyckmans and Christopher S. Chen

doi:10.1038/nmat3989

Physical cues from the extracellular environment influence the lineage commitment of stem cells. Now, experiments on human mesenchymal stem cells cultured on photodegradable hydrogels show that the cells' fate can also be determined by past physical environments.

Full text - Stem cell differentiation: Sticky mechanical memory | PDF (653 KB) - Stem cell differentiation: Sticky mechanical memory

See also: Article by Yang et al.

Stem cell differentiation: Yielding substrates for neurons - pp543–544

Emily Rhodes Lowry and Christopher E. Henderson

doi:10.1038/nmat3992

Soft culture substrates improve the yield of functional motor neurons derived from human pluripotent stem cells.

Full text - Stem cell differentiation: Yielding substrates for neurons | PDF (2,221 KB) - Stem cell differentiation: Yielding substrates for neurons

See also: Letter by Sun et al.

Materials as stem cell regulators - pp547–557

William L. Murphy, Todd C. McDevitt and Adam J. Engler

doi:10.1038/nmat3937

Inherent properties of materials, such as their adhesiveness to cells, nanotopography, stiffness, degradability or chemical functionality, can influence the fate of stem cells. This Review discusses recent evidence of how inherent material properties can be engineered to regulate stem cell decisions, as well as of signal-transduction mechanisms that convert material stimuli into biochemical signals.

Full text - Materials as stem cell regulators | PDF (6,312 KB) - Materials as stem cell regulators

Harnessing nanotopography and integrin–matrix interactions to influence stem cell fate - pp558–569

Matthew J. Dalby, Nikolaj Gadegaard and Richard O. C. Oreffo

doi:10.1038/nmat3980

Stem cells respond to nanoscale cues from the extracellular matrix or culture substrates by altering cell adhesion, which can in turn define their fate. This Review discusses how stem cell adhesion and differentiation are influenced by surface nanotopography, with a particular focus on integrin–matrix interactions and cell-adhesion-mediated signalling processes.

Full text - Harnessing nanotopography and integrin–matrix interactions to influence stem cell fate | PDF (3,468 KB) - Harnessing nanotopography and integrin–matrix interactions to influence stem cell fate

Materials for stem cell factories of the future - pp570–579

Adam D. Celiz, James G. W. Smith, Robert Langer, Daniel G. Anderson, David A. Winkler, David A. Barrett, Martyn C. Davies, Lorraine E. Young, Chris Denning and Morgan R. Alexander

doi:10.1038/nmat3972

Human pluripotent stem cells (hPSCs) have great potential for regenerative medicine, yet producing billions of hPSCs suitable for clinical use needs defined culture conditions and scalable culture systems. This Review discusses the role of high-throughput materials discovery in the development of scalable growth substrates for hPSC culture.

Full text - Materials for stem cell factories of the future | PDF (1,050 KB) - Materials for stem cell factories of the future

Hippo/YAP-mediated rigidity-dependent motor neuron differentiation of human pluripotent stem cells - pp599–604

Yubing Sun, Koh Meng Aw Yong, Luis G. Villa-Diaz, Xiaoli Zhang, Weiqiang Chen, Renee Philson, Shinuo Weng, Haoxing Xu, Paul H. Krebsbach and Jianping Fu

doi:10.1038/nmat3945

Although human pluripotent stem cells (hPSCs) can be used to regenerate neural tissues, inefficient protocols and poorly defined culture conditions have hindered their use. It is now shown that soft, micropatterned culture substrates can induce hPSCs to differentiate into motor neurons with significantly improved yields and purity in comparison to rigid substrates, and that such mechanotransductive process involves the Hippo/YAP pathway and phosphorylation of the intracellular protein Smad.

Full text - Hippo/YAP-mediated rigidity-dependent motor neuron differentiation of human pluripotent stem cells | PDF (2,579 KB) - Hippo/YAP-mediated rigidity-dependent motor neuron differentiation of human pluripotent stem cells

See also: News and Views by Lowry & Henderson

Rigidity sensing and adaptation through regulation of integrin types - pp631–637

Alberto Elosegui-Artola, Elsa Bazelliéres, Michael D. Allen, Ion Andreu, Roger Oria, Raimon Sunyer, Jennifer J. Gomm, John F. Marshall, J. Louise Jones, Xavier Trepat and Pere Roca-Cusachs

doi:10.1038/nmat3960

Cell behaviour is in part regulated by the rigidity of their environment, yet the underlying mechanisms have remained unclear. It is now shown for breast myoepithelial cells expressing two types of integrin that rigidity sensing and adaptation can be explained by a clutch-bond model that considers the different rates of binding and unbinding between the integrins and the extracellular matrix.

Full text - Rigidity sensing and adaptation through regulation of integrin types | PDF (1,637 KB) - Rigidity sensing and adaptation through regulation of integrin types

See also: News and Views by García & García

Auxetic nuclei in embryonic stem cells exiting pluripotency - pp638–644

Stefano Pagliara, Kristian Franze, Crystal R. McClain, George W. Wylde, Cynthia L. Fisher, Robin J. M. Franklin, Alexandre J. Kabla, Ulrich F. Keyser and Kevin J. Chalut

doi:10.1038/nmat3943

When exiting pluripotency but before irreversibly committing, embryonic stem cells pass through at least one transition state. It is now shown that in this metastable state the nuclei of the cells is auxetic, that is, when stretched their cross-section expands, and when compressed their cross-section contracts, and that this is in part a consequence from global chromatin de-condensation.

Full text - Auxetic nuclei in embryonic stem cells exiting pluripotency | PDF (1,341 KB) - Auxetic nuclei in embryonic stem cells exiting pluripotency

See also: News and Views by Wang

Mechanical memory and dosing influence stem cell fate - pp645–652

Chun Yang, Mark W. Tibbitt, Lena Basta and Kristi S. Anseth

doi:10.1038/nmat3889

Mechanical cues from the local cellular microenvironment can direct cell fate. Now, experiments with human mesenchymal stem cells cultured on phototunable soft poly(ethylene glycol) hydrogels show that the cells remember past physical environments—with the transcriptional co-activators YAP and TAZ acting as a mechanical rheostat—and therefore that appropriate doses of mechanical cues can be used to manipulate the cells' fate.

Full text - Mechanical memory and dosing influence stem cell fate | PDF (1,986 KB) - Mechanical memory and dosing influence stem cell fate

See also: News and Views by Eyckmans & Chen