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Cellular DNA is often torsionally constrained, but the topologies that such DNA can adopt under tensile strain have remained largely untested. Here, the authors use single-molecule optical tweezers to illustrate the structural plasticity of torsionally constrained DNA under mechanical force.

Chromosomes interact with the cell environment through their interface. Here, the authors use Atomic Force Microscopy to probe the interface and local micromechanics of the chromatin network of native human mitotic chromosomes.

Understanding how DNA bends and stretches provides insight into how the genetic information it contains is expressed. However, the role that the double-helical shape of DNA plays in determining its mechanical properties has not previously been investigated. Now, a model that incorporates DNA’s famous shape provides a better understanding of how the molecule reacts to large forces.

A method that uses a combination of optical trapping, fluorescence microscopy and microfluidics to analyse the internal structure of chromosomes shows that there is a distinct nonlinear stiffening of the chromosome in response to tension.

In anaphase, any unresolved DNA entanglements between the segregating sister chromatids can give rise to chromatin bridges. Here, the authors present an in vitro single-molecule assay that mimics chromatin under tension, to show that PICH is a tension- and ATP-dependent nucleosome remodeler.

Here the authors probe the cleavage and gate opening of single-stranded DNA by the human topoisomerase TRR using a unique single-molecule strategy to reveal structural plasticity in response to both double-stranded DNA and the helicase BLM.

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.

DNA intercalators, a type of fluorescent probes widely used to visualize DNA, can perturb DNA structure and stability. Here, the authors show how DNA-binding affinity can be tuned using DNA tension, ionic strength and dye species, and how this can be used to minimize DNA structural perturbations.

Red blood cell disorders are often accompanied by increased release of extracellular vesicles (EVs), but their structural and mechanical properties are not fully understood. Here, the authors show that red blood cell EVs show liposome-like mechanical features and are softened in blood disorder patients.

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 in cells is triggered by an increase in Ca²⁺ and involves SNARE complexes and calcium-sensing proteins, but the mechanism underlying the Ca²⁺-sensors’ role in fusion remains unclear. Here the authors show in vitro that the Ca²⁺-sensor Doc2b acts directly on membranes and induces a hemifusion intermediate in the presence of calcium.

The physical mechanisms that govern chromosomal viscoelasticity remain elusive. Here the authors combine single-chromosome manipulation and computational methods to show that their collective properties are controlled by the physico-chemical environment.

Acoustic force spectroscopy applies acoustic forces across a large dynamic range for highly multiplexed single-molecule measurements in a simple, compact setup.

A combination of single-molecule techniques shows that the repair proteins XRCC4 and XLF form heteromeric mobile sleeve-like complexes that can bridge and hold together fragments of broken DNA.

Replication of the HIV-1 viral genome can be inhibited by a protein known as APOBEC3G, via two seemingly contradictory mechanisms. Now, the molecular conundrum behind these two processes has been resolved.

How the genome is physically organized is less understood in archaea than in eubacteria or eukaryotes. Laurens et al. measure DNA binding by the Sulfolobus solfataricusproteins Alba1 and Alba2 using single-molecule techniques and conclude that the presence of Alba2 leads to more bridging between DNA.

Single DNA-binding proteins can be tracked on densely covered DNA at high spatial and temporal resolution and in the presence of high protein concentrations by using a technique that combines optical tweezers, confocal fluorescence microscopy and stimulated emission depletion (STED) nanoscopy.

A new single-molecule approach is used to examine how a nucleoid-associated protein, H-NS, functions. H-NS sits between the two DNA molecules and is aligned along the helical pitch. H-NS does not act as a barrier to RNA polymerase, and its cooperative binding ensures that H-NS is dynamic enough to accommodate the movement of DNA-associated motor proteins, but stable enough to maintain DNA loops.

DNA strand exchange results in a physical linkage between two homologous DNAs. The RecA/RAD51 family of ATPases mediates strand exchange by forming a long filament on the DNA. This paper uses a single-molecule approach to elucidate how the filament is disassembled once the strands are exchanged, and how this process relates to the energy released by nucleotide hydrolysis.

The mitochondrial transcription factor A (TFAM) mediates both mitochondrial transcription and DNA compaction, but how it achieves these two functions is unknown. In this study, TFAM is shown to slide along DNA and cause local melting, suggesting a mechanism for how TFAM modulates both transcription and compaction.

Single-molecule and biochemistry approaches are used to investigate how ultra-fine DNA bridges, which form between sister chromatids during anaphase, are recognized and processed by cellular factors PICH, BLM, TopoIIIα and RPA.

The mechanics and structural transitions of DNA are important to many essential processes inside living cells. Here the authors combine theory and single-molecule experiments to show that intercalator binding stabilises a new structural state of DNA: hyperstretched DNA.

Plasmodium falciparum secretes extracellular vesicles (EVs) while growing inside red blood cells (RBCs). Here the authors show that these EVs contain assembled and functional 20S proteasome complexes that remodel the cytoskeleton of naïve human RBCs, priming the RBCs for parasite invasion.

An in-depth characterization of single-particle active microrheology via Acoustic Force Spectroscopy shows potential to measure viscoelastic moduli spanning five orders of magnitude and local heterogeneity in collagen gels and cells.

Viruses display fascinating dynamics during their life cycle. Only recently has it become possible to probe viral dynamics at the single-particle level. This Review discusses dynamical properties of viruses and recent developments in physical virology approaches to probe such dynamics.

Mechanobiology describes how biological systems respond to mechanical stimuli. This Review surveys basic principles, advantages and limitations of applying and combining atomic force microscopy-based modalities with complementary techniques to characterize the morphology, mechanical properties and functional response of complex biological systems to mechanical cues.