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Statement of Significance (120 words): The nucleosome is the essential packaging unit of DNA. ‘Oncohistones’, which are histone mutations associated with cancer, are known to compromise the stability of the nucleosome and affect nucleosome sliding. Here we perform long-time molecular dynamics simulations of two buried histone core mutations, demonstrating that these mutations reduce the stability of the histone core at the H2B-H4 interface. Next, we demonstrate that these same mutations lower the dimer dissociation temperature and shift the nucleosome dissociation pathway using biophysical assays.

SIGNIFICANCE Magnetotactic bacteria (MTB) are microorganisms suitable for biomedical and microfluidic applications, since they are controllable with a magnetic field. However, accurately measuring their magnetic moment, a key biophysical property, remains a challenge. We thus introduce a fully automated and rigorous approach to extract magnetic moment from MTB motion in an applied magnetic field. We obtain the magnetic moment statistics for the widely used MSR-1 MTB, and clearly show that the magnetic moment scales linearly with the cell size. Our results enable differentiating between various MTB types within populations based on velocity and magnetic moment. Full automation enables magnetic moment extraction from much larger data sets than previously achieved.

Statement of Significance: Tauopathies involve pathological tau aggregation and propagation, but the minimal tau sequences capable of initiating and spreading aggregation remain unclear. This study identifies the tau fragment R2R3 as intrinsically capable of rapidly forming stable, β-sheet-rich fibrils and effectively inducing sustained intracellular aggregation. Critically, our results show that the native R2-R3 junction alone, without introduced modifications, is sufficient for robust tau aggregation and seeding activity, revealing a previously unrecognized minimal element responsible for tau pathology. This provides a streamlined experimental model for studying fundamental tau aggregation mechanisms and screening therapies targeting events associated with initial tau assembly.

Statement of significance: Here we examine how the organization of receptors and neurotransmitter release sites in inhibitory glycinergic synapses, constituting the most abundant synapses in the brain stem and spinal cord, affects synaptic function. Our work reveals that peripheral positioning of receptors can give rise to rapidly decaying currents. Moreover, it shows that a high density of receptors and placement of transmitter release sites opposed to receptor cluster centers is required to counteract this rapid decay. Put together, we thus show how the structural properties of these synapses relate to the kinetics of synaptic currents, an important step towards establishing how the post-synaptic cell would integrate excitatory and inhibitory inputs.

SIGNIFICANCE: To eradicate amyloidosis, represented by Alzheimer’s and Parkinson’s disease, a methodology for early-stage diagnosis is vital. In this study, we explore the potential of ultrasonication to protein solution as a tool for detection of amyloid seeds of α-synuclein, a promising biomarker for early diagnosis of Parkinson’s disease. The results show that ultrasonication can detect ultra-trace amyloid seeds (10 pg/mL), even in a highly crowded milieu, which cannot be detected by a conventional method. We discuss the ultrasonic effects on the seed detection from the biophysical viewpoint. The results indicate that ultrasonic cavitation plays a key role in the sensitive detection of seeds from a crowded sample. These results highlight the potential of ultrasonication as a methodology for early-stage diagnosis of amyloidosis.

Modulation of ion channels is a key mechanism by which anesthetics exert their effects. Propofol, a widely used anesthetic, has been shown to influence mechanosensitive ion channels (MSCs), though the details of this interaction remain under investigation. In this study, we show that propofol inhibits Piezo mechanosensitive channels using electrophysiological recordings and calcium imaging in HEK293T cells overexpressing human Piezo1 (hP1) and Piezo2 (hP2) channels. At 50 μM, propofol inhibited hP1 currents across multiple configurations (outside-out, whole-cell, and cell-attached) with a dissociation constant of 51.6 ± 24.0 μM.

Significance Statement: Our findings reveal the stiffness and robustness of the quantum principle-designed structure of LH2, ensuring efficient energy transfer even in the presence of environmental variations, including curved membranes. The maintenance of this exceptional structural design necessitates the optimization of vesicle sizes. This study exemplifies quantum effects in biology at various scales, spanning from the sub-ten nanometer LH2 protein complex to 50-nanometer membrane vesicles, and extending to the overall intracytoplasmic membrane morphology within bacterial cells.

Statement of Significance: This study aims to resolve a key debate on how myosin converts ATP energy into muscle contraction. With a mechanics model, we replicate a broad range of experimental observations and reveal that a gradual Pi-release that is not directly coupled with the lever arm swing may offer a route to adjust the stability of a working myosin on the actin filament, thereby modulating the power stroke to influence muscle contraction. Our findings can have broad implications for understanding muscle diseases, synthetic bioactuators, and the evolution of molecular motors.

Enzyme thermal adaptation reflects a delicate interplay between the sequence, structure, and dynamics of proteins, fine-tuning their catalytic activity to meet environmental demands. Understanding these evolutionary relationships can drive advances in bioengineering, including the design of industrial enzymes and the development of novel therapeutics. This work explores sequence-to-dynamics connections in subtilisin-like serine protease homologs using a recently developed computational methodology that employs expanded ensemble simulations and temperature-sensitive contact analysis.

The survival of microorganisms crucially depends on the nature of their interactions with other cohabiting microorganisms. Often these interactions are mediated via chemical signals, and the role of physical factors is overlooked. In this study, we probe into the spreading characteristics of Pseudomonas aeruginosa, a flagellated bacteria in moisture-limited conditions and in the presence of immotile yeast colonies of Cryptococcus neoformans—a duo commonly known to cohabitate in nature. We find that bacteria spread faster in the presence of yeast, caused by the enhanced motility of bacterial cells in the vicinity of the yeast microcolonies.

Significance Statement — Proteins and DNA in the nucleus display rich spatial organization, but the forces which drive it are not well understood. Here we show that proteins prone to forming condensed liquid droplets can drive configurational phase transitions of long polymers, like DNA, even when too dilute to phase separate on their own. Indeed, many transcription factors (TFs) will condense into liquid phases in the absence of DNA when enriched to much higher concentrations than in the nucleus. With DNA, and at much lower TF concentrations, we expect these proteins to undergo generalized prewetting transitions, leading to abrupt changes in the three dimensional organization of chromatin. We argue that these phase transitions play an important role in organizing and regulating chromatin.