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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.

Cochlear outer hair cells (OHCs) have two mechanosensitive elements: the hair bundle with mechanotrasducer channels and the piezoelectric lateral wall of the cell body. The present report examines how these elements interact with each other by incorporating OHCs into the simplest local cochlear models. In the frequency range, typically above 1 kHz, where capacitive conductance is greater than the ionic conductance, hair bundle (HB) conductance drives the piezoelectric cell body and amplified oscillation by countering viscous drag, while the cell body increases its stiffness owing to strain-induced polarization, elevating the resonance frequency.

Resurgent sodium currents (INaR) result from an unorthodox gating behavior of voltage-activated sodium channels (NaV), allowing transient re-openings during repolarization from an apparently inactivated state. In both native cells not normally exhibiting INaR and in heterologous expression systems, intracellular delivery of small positively charged peptides through the recording pipette elicits robust INaR, suggesting that INaR arises from a peptide-mediated open-channel block that is relieved upon repolarization.

SIGNIFICANCE: 2Danalysis is a significant contribution for the systematic analysis of membrane and biopolymers simulations at planar interfaces. Developed under the open-source MDAKit framework, it enables efficient analysis of trajectories and provides versatile tools for projecting biophysical properties onto a two-dimensional plane. These capabilities enhance the visualization of spatial and temporal changes in membrane characteristics, such as order parameters, and support the study of biopolymer-surface interactions by analyzing adsorption and confinement mechanisms at 2D interfaces. The users can customize the toolbox to study complex 2D phenomena from molecular simulation.

The interaction of cell-free DNA with biological particles has been linked to autoimmune diseases such as systemic lupus erythematosus, but mechanistic details are lacking. Our recent work has shown that DNA adsorbed on the surface of synthetic particles, forming a DNA “corona,” leads to an enhanced immunostimulatory response in macrophages, providing a model system to understand how DNA-particle interactions may lead to autoimmune diseases. This current study provides a detailed examination of DNA (500-600 base pairs and ∼10,000 base pairs) interacting with synthetic particles (40 nm - 10 μm) and planar surfaces.

Single particle tracking (SPT) is a powerful technique for probing the diverse physical properties of the cytoplasm. Genetically encoded nanoparticles provide an especially convenient tool for such investigations, as they can be expressed and tracked in cells via fluorescence. Among these, 40-nm GEMs provide a unique opportunity to explore the cytoplasm. Their size corresponds to that of ribosomes and big protein complexes, allowing us to investigate the effects of the cytoplasm on the diffusivity of these objects while excluding the influence of chemical interactions during stressful events and pathological conditions.

(Biophysical Journal 121, 705–714; March 1, 2022)

Myosin-based regulation has emerged as a fundamental new concept governing both cardiac and skeletal muscle contractile function during both health and disease states. Myosin-targeted therapeutics have the potential to treat both heart failure with systolic or diastolic dysfunction based on either activating or inhibiting the function of myosin. In this study we developed a striated muscle myosin-specific high-affinity peptide targeted towards the proximal subfragment-2 (S2) region of the MYH7 myosin, which has been shown to undergo conformational changes associated with force generation by the myosin head domains.