Search

An expert recommendation is presented for the design and evaluation of research studies using transcranial electrical stimulation, resulting in the selection of a 66-point checklist aimed at improving the quality of transcranial electrical stimulation studies.

To understand enzymatic redox reaction mechanisms, it is important to investigate the redox behavior at the metal centers. This Protocol describes metalloenzyme attachment to electrodes and how to perform X-ray absorption spectroelectrochemistry.

Protein complexes are essential for cell function. Here, authors show that paired ribosomes can help each other’s nascent chains fold correctly, enabling proper dimer assembly and preventing misfolding, using lamin as a model system.

Single-stranded DNA-binding proteins protect exposed DNA during replication but create potential barriers for polymerases. Here, the authors reveal that DNA polymerase actively and sequentially displaces stationary SSB proteins. The SSB C-terminal tail facilitates this process by reducing energy barriers for displacement to ensure DNA replication.

Reported wearable dry electrodes have limited long-term use due to their imperfect skin compliance and high motion artifacts. Here, the authors report an intrinsically conductive, stretchable polymer dry electrode with excellent self-adhesiveness for long-term high-quality biopotential detection.

Chromosomes are coated in proteins and RNA called the mitotic chromosome periphery. Here, broadband microrheology analysis has shown that this coat has dynamic, liquid-like properties and provides an external structural constraint.

3D ovarian elasticity mapping reveals distinct spatial elasticity patterns in follicles and corpora lutea, age-related changes, and potential correlations with cellular phenotypes and matrix composition.

Whether and how cells measure and regulate their adhesion in response to the extracellular matrix area is unknown. Here, the authors show that cells adhering to restricted matrix protein areas exhibit a spatially enhanced adhesion state with much higher force per unit area compared to cells on larger areas.

The authors present a sample preparation method for biological cryo-EM that offers advantages over existing blotting methods, such as reduced variability, no need for expensive instrumentation and improved particle orientation distributions.

The human mitochondrial helicase Twinkle is essential for maintaining mitochondrial DNA. Here, the authors combine biochemical and single-molecule approaches to show how Twinkle’s real-time kinetics are regulated by its amino and carboxyl terminal domains, revealing a key auto-regulatory mechanism.

Optical tweezers based on focused laser beams are widely used for biophysical measurements of single molecules in vitro. Here Zhong et al. use infrared optical tweezers to trap and manipulate red blood cells within subdermal capillaries in living mice.

Molecular glues have great potential for drug discovery if they can be systematically discovered. Konstantinidou, et al describe a scaffold-hopping approach using multicomponent reaction chemistry to design molecular glues that induce 14-3- 3σ/ERα formation in cells.

Precise assembly of undecorated colloids demands a clever approach. Here, the authors draw unlikely inspiration from vector graphics to direct colloids into 2D structures, pinning the ends and corners of assembled patterns with optical tweezers and manipulating the segments like vectors.

Cellular forces shaping cells and tissues during development are well understood, but their dynamic material properties less so. Here, the authors use Brillouin microscopy to map cell material properties in developing fruit fly embryos, revealing dynamic, fate-specific modulation.

A high-peak-power low-duty-cycle pulsed fibre laser enables stimulated Brillouin scattering microscopy with pixel dwell times as low as 0.2 ms and spatial resolution as low as 500 nm and 2 μm in the lateral and axial directions, respectively.

Sample orientation is crucial to ensure optimal image quality in light microscopy. Here the authors enable multi-axis orientation of fixed mouse embryos and shrimp, and live zebrafish embryos and larvae by introducing magnetic beads and rotating the sample with a magnetic field in a microscope.

This paper reports an analytical method for single-particle tracking data. It identifies diffusive states of intracellular proteins and the rates of transition between them.

The neural circuits of the vestibular system, which detects gravity and motion, remain incompletely characterised. Here the authors use an optical trap to manipulate otoliths (ear stones) in zebrafish larvae, and elicit corrective tail movements and eye rolling, thus establishing a method for mapping vestibular processing.

Single-molecule studies allow biological processes to be examined one molecule at a time, as they occur. Here, zero-mode waveguides have been used to concentrate reactions in zeptolitre-sized volumes, making it possible to study real-time translocation by the ribosome. The binding of transfer RNAs (tRNAs) to the ribosome could be followed; the results show that tRNA release from the exit site is uncoupled from tRNA binding to the aminoacyl-tRNA site.

Epithelial cell–cell contact resistance to mechanical stress is defined by a regulated viscous dissipation through the cytoskeleton, where the toughness of the cell junction is set by the balance between cortical tension and cell shape recovery time.

The accelerated liquid–gel transition of collagen induced by an inert crowding agent enables the rapid and versatile fabrication of collagenous tissues under biocompatible and bioactive conditions for tissue engineering applications.

Particle tracking with ultra-high resolution in optical and magnetic tweezers has so far relied on laser detection through photodiodes. Here, Huhle et al. demonstrate three-dimensional particle tracking with Ångström accuracy and real-time GPU-accelerated data processing at kHz rates using camera-based imaging.

Using single-molecule force spectroscopy, the authors demonstrate that proline isomerization and cysteine-mediated disulfide bonds lead to distinct mechanical states of the titin I-band immunoglobulin-like domains within the physiological force range.

Using cryo-EM structures and electrophysiological analysis of Arabidopsis CNGC1 and CNGC5, this study characterizes plant CNGCs as a class of CNBD channels that feature Ca²⁺ selectivity and are not regulated by cyclic nucleotide monophosphate binding.

Nona Sotoodehnia and colleagues report a meta-analysis of 14 genome-wide association studies for QRS interval, an electrocardiogram measurement of cardiac ventricular conduction. They identify 22 loci associated with QRS duration.

Light-controlled motor–microtubule systems are used to construct micrometre-scale fluid flows for programmable transport, separation and mixing.

The authors present a computational framework that leverages mechanical force inference and spatial transcriptomics to enable analyses of the interplay between the transcriptomic and mechanical state.

Structural characterization of protein complexes is challenging for low-input samples. Here, authors develop a SNAP-MS mass spectrometry workflow based on dissolvable hydrogel beads to enable efficient purification and native-MS-based analysis from biological samples.

Design of cysteine-targeting analogs of a reversible SETDB1 triple Tudor domain (3TD) ligand, UNC6535, led to UNC10013, a potent covalent ligand with high selectivity. UNC10013 demonstrated allosteric inhibition of SETDB1-mediated Akt methylation in cells, a promising approach to SETDB1 therapeutics.

TRPV1 ion channels allow for water flow through them and their activity can be suppressed by downregulating the permeation of cations through the channels via the administration of deuterated water.

Despite the success of PD-1 blockade in cancer therapy, how PD-1 initiates signalling remains unclear. Here the authors show that PD-1 function is reduced when mechanical support on ligand is removed.

Collisional mixing of lipids in SMA or DIBMALPs has been shown recently. Here, authors show proteins in these nanoparticles also undergo mixing, allowing for study of intramembrane proteolysis in lipid-polymer nanoparticles.

Cellular target engagement technologies enable quantification of intracellular drug binding, but the simultaneous assessment of drug-associated phenotypes is challenging. Here, the authors develop CeTEAM (cellular target engagement by accumulation of mutant), a platform that can simultaneously evaluate drug-target interactions and phenotypic responses for holistic assessment of drug pharmacology using conditionally stabilized drug biosensors.

The authors directly quantify the tension-dependent lifetimes of homo- and hetero-dimers of human α-actinins, revealing an ultra-high mechanical stability of the dimers within physiological tension range under shear-stretching geometry.

Toll-like receptors are key mediators of immune responses, but gaps remain in understanding their signalling. Here, the authors introduce an optical biosensor assay to detect real-time TLR activation and signalling dynamics, uncovering signalling signatures that may aid future drug design.

DNA polymerase engages with DNA in various ways during replication. Using mechanical DNA manipulation and single-molecule fluorescence the authors show that replication is dynamic. Bursts of polymerase activity interspersed with protein exchanges and a memory effect can be observed, during replication.

Membrane fusion is crucial for fabricating artificial membranes. Here, the authors present an approach combining electric field with hydraulic pressure to physically control the fusion, enabling tuning of the shape and size of the 3D freestanding lipid bilayers in physiological solutions.

Single DNA molecules can be detected in aqueous solutions at ambient temperatures by electron spin resonance spectroscopy with diamond sensors.

A thermophoretic trapping approach enables users to observe the behavior of single amyloid fibrils in solution for hours without any immobilization.

A rapid sample mixing approach enables time-resolved structural studies of enzymatic reactions using serial synchrotron crystallography.

FluidFM-based force-controlled nanopipettes enable control of mechanical stimuli for the investigation of Piezo1-induced mechanosensation in cell membranes.

Intrinsically disordered proteins are frequently dysregulated in many diseases, but because of their heterogeneous, highly dynamic structural states they have been considered largely ‘undruggable’ by traditional approaches. This Review proposes that a synergy of advanced experimental and computational approaches will help to overcome this barrier to drug discovery.

In cerebral cavernous malformations, mutant cells recruit healthy endothelial cells to form mosaic lesions. Here, the authors show that mutant cells can hijack and reprogram neighboring wildtype cells by mechanically pulling on them.

Controlled manipulation of cultured cells by delivery of exogenous macromolecules is a cornerstone of experimental biology. Here, the authors describe a platform to deliver defined numbers of macromolecules into cultured cell lines at single molecule resolution.

The organization of membrane proteins is critical to cellular function. Here the authors explore how computational protein design, MD simulation, and cell-free systems can be combined to elucidate how membrane-protein hydrophobic mismatch affects protein folding and organization in synthetic lipid membranes.