Volume 13 Issue 6, June 2014

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.

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

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.

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.

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

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.

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.

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.

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.

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.

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 Na_5/8MnO₂ are coupled to an unusual ordering of Na vacancies.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.