Biological techniques

Here the authors fabricate a fibre-coupled electrode ‘fibertrode’ that integrates light emission sites and platinum microelectrodes on tapered optical fibre neural implants, for combined stimulation and recording of neural activity over small brain volumes in vivo with reduced photoelectric artefacts.

Precise manipulation of colloids and cells is desired for material and life sciences. However, such control remains challenging without material modifications. Here, the authors achieve reversible single-particle manipulation with subwavelength resolution and high throughput using harmonic acoustics.

The influence of stress relaxation of the extracellular matrix on the formation of intestinal organoids was investigated. It was shown that a stress-relaxing synthetic matrix promotes crypt budding through increased symmetry breaking and niche cell formation.

An erbium(III)–bacteriochlorin probe with large Stokes shift and efficient near-infrared to near-infrared energy conversion enables multiplexed imaging of deep tissues in living animals.

This Review highlights the progress that has been made in the development of diagnostic tools for the detection of SARS-CoV-2 in the fight against COVID-19.

This perspective describes recent developments in genetically encoded protein contrast agents for non-invasive biological imaging, namely ultrasound, magnetic resonance and optoacoustic imaging modalities.

It is now shown that tumour-associated macrophages recruited early during tumour evolution stimulate stromal fibroblasts to express collagen crosslinking enzymes and that the stromal expression, particularly of lysyl hydroxylase 2, can predict survival in a patient cohort.

This Review highlights approaches used to generate somatic cell-derived organoids for modelling epithelial tissue to understand disease progression and how they are employed in preclinical drug screening.

A laser-based patterning method enables the fast fabrication of high-quality two- and three-dimensional features in polydimethylsiloxane for microfluidics and biomedical applications.

Mechanical properties and forces sculpt the behaviour of cells in living organisms. Silicon-based nanochips implanted into mouse one-cell embryos have been used to reveal mechanical changes during the early onset of embryonic development.

Atomic force microscopy indentation measurements of cells cultured on soft substrates may result in an underestimation of cell stiffness. A model has now been developed that takes this soft substrate effect into account, revealing that cortical cell stiffness is largely independent of substrate mechanics.

As in haematopoietic cells and platelets, agonist binding to protease-activated receptors PAR1 and PAR2 in non-haematopoietic cells also triggers signalling pathways that lead to α₅β₁-integrin-mediated cell adhesion.

A mechanism of cell response to localized tension shows that syndecan-4 synergizes with EGFR to elicit a mechanosignalling cascade that leads to adaptive cell stiffening through PI3K/kindlin-2 mediated integrin activation.

Lamin mutations responsible for muscular dystrophy are shown to reduce nuclear envelope stability, resulting in mechanically induced nuclear envelope rupture, DNA damage and activation of DNA damage response pathways that lead to muscle cell death. Preventing nuclear envelope damage by reducing cytoskeletal forces on the nucleus improves muscle fibre health and function.

Anticancer drugs such as Taxol can affect microtubule dynamics and organization in cells. Direct visualization of the action of such drugs has shown that they can trigger local and cooperative changes in microtubule lattice and induce formation of stable microtubule regions that promote rescues.

High-spatial-resolution mechanical imaging reveals that intracellular forces generate cellular nanoscale stiffness patterns.

Crosstalk between microtubules and the actin cytoskeleton of cells is important in elucidating integrin-mediated adhesion and mechanotransduction. It is now shown that microtubule-mediated control of focal adhesions and podosomes occurs via KANK family proteins.

Arrays of graphene microtransistors are used to record infraslow cortical brain activity. The reduced signal drift and the array compatibility with optical imaging techniques make these devices useful for monitoring of brain physiology.

A fluorescence-activated cell sorter is used to purify microparticles from colloidal mixtures.

Nanoparticle diffusion in the cytoplasm of living cells strongly deviates from random motion. Single-particle tracking analysis show that this is due to non-specific interactions with intracellular components.

Gas-filled vesicles derived from photosynthetic microbes are shown to elicit magnetic resonance imaging contrast in vitro and in vivo with the potential for acoustically modulated multiplexing and molecular sensing.

The mechanism by which cell geometry regulates cell signalling is reported to be modulated by lipid rafts within the plasma membrane, which are now shown to be responsible for geometry-dependent mesenchymal stem cell differentiation.

Angiogenesis has been implicated in fibrotic diseases of the liver. Here, the authors developed microniches that mimic angiogenesis during different stages of liver fibrosis, and demonstrate the role of mechanotransduction in fibrogenesis.

Integrins play an important role in the adhesion of cells to their matrix. Here, the authors investigate how fibroblasts respond to mechanical loads, at the onset of cell adhesion to fibronectin, in distinct phases that are modulated by integrins.

A microfluidics method to generate giant, copolymer-stabilized liposomes is presented. These vesicles are functionalized with distinct proteins to recapitulate cellular processes.

Circulating tumour DNA is used as a biomarker for cancer diagnosis. Here, the authors identified a DNA methylation biomarker for hepatocellular carcinoma and developed diagnostic and prognostic models to predict specificity and survival of patients.

Heart-on-a-chip devices with integrated strain gauges for direct readout of tissue contractile strength allow for multiplexed drug-dose experiments and studies of functional maturation of cardiac tissue.

A high-throughput hydrogel-based platelet-contraction cytometer is able to quantify single-platelet contraction forces and may function as a clinical diagnostic biophysical biomarker.

This Review discusses the materials and electronic requirements for flexible sensors and electronic systems to mimic the mechanical and sensing properties of natural skin, with the goal of providing artificial prostheses with sensing capabilities.

A biocompatible and biodegradable mesostructured form of silicon is used to make lipid-bilayer-supported bioelectric interfaces that can optically modulate the electrophysiology of single dorsal root ganglia neurons.

A highly sensitive plasmonic biosensor, based on hyperbolic metamaterials, can detect biomolecules of ultralow molecular weight at picomolar concentrations.

The confinement imposed by the three-dimensional microenvironment promotes the induction of pluripotency in somatic cells through an accelerated mesenchymal-to-epithelial transition and increased epigenetic remodelling.

Plasmonic nanostructures are known to be an attractive platform for highly sensitive molecular sensors, although they often lack specificity. A plasmonic device with a sharp optical resonance tuned to biomolecules selectively captured on the surface of the device now offers a versatile yet highly specific platform for molecular sensing.

The in vivo optical detection of bacterial infections requires highly specific imaging probes with small affinity to mammalian tissue. It is now shown that fluorescent dyes that are conjugated to maltohexaose can be internalized rapidly via the bacteria-specific maltodextrin transport pathway, enabling the in vivo imaging of Escherichia coli down to 10⁵ colony-forming units.

On standard tissue culture platforms, mesenchymal stem cells tend to spontaneously differentiate with the loss of multi-lineage potential. Now, a robust and reproducible nanotopographical platform has been shown to maintain stem cell phenotype and promote stem cell growth over several months whilst implicating mechanisms for the observed stem cell behaviour

A one-pot, high-throughput method for the recombinant polymerization of monomer DNA sequences is reported. The method enables the rapid synthesis of diverse libraries of artificial repetitive polypeptides, exemplified by the isolation of protease-responsive polymers and a family of polypeptides with reversible thermally responsive behaviour.