Table of contents

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 & 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 and Views

Cellular mechanotransduction: Sensing rigidity pp539 - 540

José R. García & 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 & 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 & 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.

Layered materials: Scaling up exfoliation pp545 - 546

James M. Tour


High-shear mixing is now shown to be an effective approach for the exfoliation of large quantities of graphene and other two-dimensional materials, providing a viable route for the industrial scaling of applications based on these layered crystals.

See also: Article by Paton et al.



Correction p546



News and Views

Material witness: In the footsteps of the sea stars p546

Philip Ball




Materials as stem cell regulators pp547 - 557

William L. Murphy, Todd C. McDevitt & 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 & 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 & 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.



Singular robust room-temperature spin response from topological Dirac fermions pp580 - 585

Lukas Zhao, Haiming Deng, Inna Korzhovska, Zhiyi Chen, Marcin Konczykowski, Andrzej Hruban, Vadim Oganesyan & Lia Krusin-Elbaum


The surface electronic states associated with topological insulators have attracted considerable attention due to their robust nature. Using low-field susceptibility measurements, a paramagnetic singularity that is common to the (Bi,Sn)2(Se,Te)3 family of topological insulators is observed, and explained in terms of the topological surface states.

Direct visualization of the Jahn–Teller effect coupled to Na ordering in Na5/8MnO2 pp586 - 592

Xin Li, Xiaohua Ma, Dong Su, Lei Liu, Robin Chisnell, Shyue Ping Ong, Hailong Chen, Alexandra Toumar, Juan-Carlos Idrobo, Yuechuan Lei, Jianming Bai, Feng Wang, Jeffrey W. Lynn, Young S. Lee & Gerbrand Ceder


The Jahn–Teller distortion is an electronic effect that is known to couple charge, orbital and magnetic ordering phenomena in many complex solids. Using a combination of scattering and microscopy approaches, it is now shown that cooperative Jahn–Teller distortions in Na5/8MnO2 are coupled to an unusual ordering of Na vacancies.

Printing-based assembly of quadruple-junction four-terminal microscale solar cells and their use in high-efficiency modules pp593 - 598

Xing Sheng, Christopher A. Bower, Salvatore Bonafede, John W. Wilson, Brent Fisher, Matthew Meitl, Homan Yuen, Shuodao Wang, Ling Shen, Anthony R. Banks, Christopher J. Corcoran, Ralph G. Nuzzo, Scott Burroughs & John A. Rogers


A strategy to overcome the maximum theoretical efficiency limit of single-junction solar cells is to realize stacked, multi-junction cells that are used under highly concentrated light. Now, a printing-based, scalable approach for the assembly of multi-junction solar cells in concentrator photovoltaic modules that reach a high power conversion efficiency is reported.

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 & 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



Spatially resolving valley quantum interference of a donor in silicon pp605 - 610

J. Salfi, J. A. Mol, R. Rahman, G. Klimeck, M. Y. Simmons, L. C. L. Hollenberg & S. Rogge


The valley degree of freedom has been proposed as a means to encode information in a number of condensed-matter systems. Now, detailed scanning tunnelling microscopy measurements are used to spatially resolve the valleys associated with a single donor qubit in silicon.

Observation of quadrupole helix chirality and its domain structure in DyFe3(BO3)4 pp611 - 618

T. Usui, Y. Tanaka, H. Nakajima, M. Taguchi, A. Chainani, M. Oura, S. Shin, N. Katayama, H. Sawa, Y. Wakabayashi & T. Kimura


In addition to the structural chirality of materials, there has recently been a rise in interest in the chirality arising from their magnetic and electronic structure. Using a spatially resolved resonant X-ray diffraction technique, a helical arrangement of the Dy 4f quadrupole moments in the ferroborate system DyFe3(BO3)4 is uncovered.

Proton switch for modulating oxygen reduction by a copper electrocatalyst embedded in a hybrid bilayer membrane pp619 - 623

Christopher J. Barile, Edmund C. M. Tse, Ying Li, Thomas B. Sobyra, Steven C. Zimmerman, Ali Hosseini & Andrew A. Gewirth


Molecular switches regulate many fundamental processes in natural and artificial systems. An electrochemical platform in which a proton carrier switches the activity of a catalyst is now presented. A hybrid bilayer membrane allows the regulation of proton transport to a Cu-based molecular oxygen reduction reaction catalyst.

Scalable production of large quantities of defect-free few-layer graphene by shear exfoliation in liquids pp624 - 630

Keith R. Paton, Eswaraiah Varrla, Claudia Backes, Ronan J. Smith, Umar Khan, Arlene O’Neill, Conor Boland, Mustafa Lotya, Oana M. Istrate, Paul King, Tom Higgins, Sebastian Barwich, Peter May, Pawel Puczkarski, Iftikhar Ahmed, Matthias Moebius, Henrik Pettersson, Edmund Long, João Coelho, Sean E. O’Brien, Eva K. McGuire, Beatriz Mendoza Sanchez, Georg S. Duesberg, Niall McEvoy, Timothy J. Pennycook, Clive Downing, Alison Crossley, Valeria Nicolosi & Jonathan N. Coleman


Methods to achieve large-scale production of defect-free graphene are needed to enable the commercial development of graphene-based devices. It is now shown that high-shear mixing is an effective way to exfoliate graphene and other two-dimensional materials in liquid volumes up to hundreds of litres.

See also: News and Views by Tour

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

Alberto Elosegui-Artola, Elsa Bazellières, Michael D. Allen, Ion Andreu, Roger Oria, Raimon Sunyer, Jennifer J. Gomm, John F. Marshall, J. Louise Jones, Xavier Trepat & 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 & 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 & 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

Injectable and bioresponsive hydrogels for on-demand matrix metalloproteinase inhibition pp653 - 661

Brendan P. Purcell, David Lobb, Manoj B. Charati, Shauna M. Dorsey, Ryan J. Wade, Kia N. Zellars, Heather Doviak, Sara Pettaway, Christina B. Logdon, James A. Shuman, Parker D. Freels, Joseph H. Gorman III, Robert C. Gorman, Francis G. Spinale & Jason A. Burdick


Excessive activity of matrix metalloproteinases (MMPs) occurs in many diseases; however, the systemic administration of MMP inhibitors can cause undesirable, off-target effects and hence, clinical translation has been hampered. Now, injectable polysaccharide-based hydrogels are shown to enable the localized delivery of an inhibitor of MMP following the hydrogels’ degradation in response to MMP activity. This targeted approach shows efficacy in a myocardial infarction model in large animals.



Corrigendum: Semi-metallic polymers p662

Olga Bubnova, Zia Ullah Khan, Hui Wang, Slawomir Braun, Drew R. Evans, Manrico Fabretto, Pejman Hojati-Talemi, Daniel Dagnelund, Jean-Baptiste Arlin, Yves H. Geerts, Simon Desbief, Dag W. Breiby, Jens W. Andreasen, Roberto Lazzaroni, Weimin M. Chen, Igor Zozoulenko, Mats Fahlman, Peter J. Murphy, Magnus Berggren & Xavier Crispin


Corrigendum: Ultrastable glasses from in silico vapour deposition p662

Sadanand Singh, M. D. Ediger & Juan J. de Pablo