Cell culture

Materials for cell culture — engineered substrates, animal-derived extracellular matrix and its synthetic mimics — are essential for the understanding and manipulation of cellular processes such as proliferation, migration and differentiation. In this focus issue we highlight recent developments in cellular mechanobiology and in materials for stem cell culture.



Mechanobiology in harness p531


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.



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

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


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.


News & Views

Cellular mechanotransduction: Sensing rigidity pp539–540

José R. García and Andrés J. García


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

See also: Article by Elosegui-Artola et al.

Stem cell mechanics: Auxetic nuclei pp540–542

Ning Wang


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.

See also: Article by Pagliara et al.

Stem cell differentiation: Sticky mechanical memory pp542–543

Jeroen Eyckmans and Christopher S. Chen


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.

See also: Article by Yang et al.

Stem cell differentiation: Yielding substrates for neurons pp543–544

Emily Rhodes Lowry and Christopher E. Henderson


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

See also: Letter by Sun et al.


Review Article

Materials as stem cell regulators pp547–557

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


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.

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

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


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.

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


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.



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


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.

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


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.

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


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.

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


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.

See also: News and Views by Eyckmans & Chen

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