Biophysical journal最新文献

{"title":"DNA coronas resist nuclease degradation.","authors":"Faisal Anees, Diego A Montoya, David S Pisetsky, Tariq Khan, Abhishek Kalpattu, Christine K Payne","doi":"10.1016/j.bpj.2025.05.028","DOIUrl":"10.1016/j.bpj.2025.05.028","url":null,"abstract":"<p><p>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 to 10 μm) and planar surfaces. Of specific interest is how DNA adsorbed on the surface of particles is resistant to degradation by DNase 1, a common nuclease. DNA-particle complexes are characterized by a colorimetric DNA concentration assay (PicoGreen), spectroscopy (NanoDrop), dynamic light scattering (DLS), confocal fluorescence microscopy, and transmission electron microscopy. These studies show that the protective effect of the particle is size dependent, with smaller (40 and 200 nm) particles providing less protection. Correlated with this lack of protection is significantly increased particle aggregation, suggesting that a DNA corona formed on the larger particles is protective, whereas particle aggregation, which dominates the smaller particles, is not protective. The formation of a single-stranded DNA corona leads to the opposite protective effect, with smaller (200 nm) particles leading to near-complete protection of DNA from nuclease degradation. Overall, this study provides an important biophysical basis for the interaction of DNA with particles with the goal of guiding future in vitro and in vivo studies of cell-free DNA and particles in autoimmune disease.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"2253-2262"},"PeriodicalIF":3.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein-DNA co-condensation is prewetting to a collapsed polymer.","authors":"Mason N Rouches, Benjamin B Machta","doi":"10.1016/j.bpj.2025.05.031","DOIUrl":"10.1016/j.bpj.2025.05.031","url":null,"abstract":"<p><p>The three-dimensional organization of chromatin is thought to play an important role in controlling gene expression. Specificity in expression is achieved through the interaction of transcription factors and other nuclear proteins with particular sequences of DNA. At unphysiological concentrations, many of these nuclear proteins can phase separate in the absence of DNA. In vivo, the thermodynamic forces driving these phases lead the chromosome to co-condense with nuclear proteins. However, it is unclear how DNA, itself a long polymer subject to configurational transitions, interacts with three-dimensional protein phases. Here, we show that a long compressible polymer can be coupled to interacting protein mixtures, leading to a generalized prewetting transition where polymer collapse is coincident with a locally stabilized liquid droplet. We use lattice Monte-Carlo simulations and a mean-field theory to show that these phases can be stable even in regimes where both polymer collapse and coexisting liquid phases are unstable in isolation and that these new transitions can be either abrupt or continuous. For polymers with internal linear structure, we further show that changes in the concentration of bulk components can lead to changes in three-dimensional polymer structure. In the nucleus, there are many distinct proteins that interact with many different regions of chromatin, potentially giving rise to many different prewet phases. The simple systems we consider here highlight chromatin's role as a lower-dimensional surface whose interactions with proteins are required for these novel phases.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"2280-2290"},"PeriodicalIF":3.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural and thermodynamic impact of oncogenic mutations on the nucleosome core particle.","authors":"Augustine C Onyema, Christopher DiForte, Rutika Patel, Sébastien F Poget, Sharon M Loverde","doi":"10.1016/j.bpj.2025.06.011","DOIUrl":"10.1016/j.bpj.2025.06.011","url":null,"abstract":"<p><p>The nucleosome core particle is essential for chromatin structure and function, serving as the fundamental unit of eukaryotic chromatin. Oncogenic mutations in core histones disrupt chromatin dynamics, altering DNA repair and transcription processes. Here, we investigate the molecular consequences of two mutations-H2BE76K and H4R92T-using 36 μs of all-atom molecular dynamics simulations and experimental biophysical assays. These mutations destabilize the H2B-H4 interface by disrupting critical salt bridges and hydrogen bonds, reducing binding free energy at this interface. Principal-component analysis reveals altered helix conformations and increased interhelical distances in mutant systems. Thermal stability assays and differential scanning calorimetry confirm that these mutations lower the dimer dissociation temperature and reduce enthalpy compared with the wild-type. Taken together, our results elucidate how these mutations compromise nucleosome stability and propose mechanisms through which they could modulate chromatin accessibility and gene dysregulation in cancer.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"2362-2379"},"PeriodicalIF":3.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of open-channel blocking peptides in Na_V1.5 ΔKPQ.","authors":"Maria Riedersberger, Madalina Woltereck, Paul J Wagner, Kristin Focke, Sarina Höller, Angelika Lampert, Christian Alzheimer, Stefan Düsterhöft, Tobias Huth","doi":"10.1016/j.bpj.2025.05.030","DOIUrl":"10.1016/j.bpj.2025.05.030","url":null,"abstract":"<p><p>Resurgent sodium currents (INaRs) result from an unorthodox gating behavior of voltage-activated sodium channels (Na_V), 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 INaRs, suggesting that INaRs arise from a peptide-mediated open-channel block that is relieved upon repolarization. Here we examined the hNa_V1.5 ΔKPQ mutant, which causes a long QT syndrome in the heart, to probe the open-channel block hypothesis of INaR in a channel with altered inactivation properties due to the deletion near the canonical inactivation gate. We investigated INaRs with peptides derived from the hNa_Vβ4 subunit, FGF13-1a and FGF14-1a, using the HEK293T expression system. Surprisingly, the peptides not only gave rise to pronounced INaRs with unusually fast kinetics but also altered the late sodium current of the channel mutant. To elucidate the molecular basis of these effects, we employed AlphaFold modeling of hNa_V1.5, incorporating the ΔKPQ mutation and the β4 peptide. This model supports the open-channel block mechanism of INaR and its mutual exclusivity with fast inactivation. It also demonstrates a lack of interaction between the IFM linker and the C-terminal domain in hNa_V1.5 ΔKPQ, offering a plausible explanation for why the peptides are capable of affecting both INaR and persistent currents (INaPs). Finally, the peptides generated a considerable increase in repolarization-associated Na⁺ currents with the ΔKPQ mutant, highlighting the presumed impact of pathologically enhanced INaR on cardiac electrophysiology.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"2263-2279"},"PeriodicalIF":3.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrinsic aggregation and propagation of unmodified tau peptides: R2R3 as a minimal model system.","authors":"Viswanath Das, Luisa Diomede, Lukáš Malina, Michele Mosconi, Narendran Annadurai","doi":"10.1016/j.bpj.2025.06.009","DOIUrl":"10.1016/j.bpj.2025.06.009","url":null,"abstract":"<p><p>Tau aggregation into neurofibrillary tangles is a defining feature of Alzheimer's disease and other tauopathies. Although aggregation depends largely on specific amyloidogenic motifs (particularly VQIINK and VQIVYK) in repeated regions of tau microtubule-binding domains, how the primary sequence of adjacent repeats intrinsically influences aggregation and prion-like propagation remains unclear. This study systematically characterized three unmodified, physiologically relevant tau peptide constructs-R1R3, R2R3, and R3R4-to define their intrinsic aggregation kinetics, structural features, and prion-like seeding activity. Among these constructs, we found that R2R3 showed rapid aggregation, distinct β-sheet formation, and potent seeding capable of sustained secondary propagation in cellular biosensor assays. Whereas recent studies have highlighted chemically modified peptides (e.g., acetylated and phosphomimic peptides), our study emphasizes the importance of native, unmodified sequences as fundamental determinants in tau aggregation. Furthermore, these findings establish R2R3 as a robust minimal tau model, providing a valuable tool for mechanistic research and therapeutic screening in tau-related neurodegeneration.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"2339-2346"},"PeriodicalIF":3.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Viscosity and density measurements on the cytosol of human red blood cells.","authors":"Thomas John,Karin Kretsch,Felix Milan Maurer,Steffen Michael Recktenwald,Lars Keastner,Christian Wagner","doi":"10.1016/j.bpj.2025.07.002","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.07.002","url":null,"abstract":"We introduce an approach for determining the viscosity of the intracellular liquid, called cytosol, of human red blood cells (RBCs). This methodology combines measurements of the mass density distribution of RBCs and the viscosity of the cytosol relative to its water content. The density distribution is obtained through buoyant density centrifugation paired with cell counting. By correlating the Gaussian distribution of cell population densities with the viscosity-density relationship of the cytosol, we derive a log-normal distribution of the cytosol viscosity in healthy RBCs. The viscosity contrast λ=η/ηplasma, which is the ratio between viscosities of the RBC cytosol and blood plasma under physiological conditions, is found to have a mean value of . This value is notably higher than those cited in existing literature for numerical simulations. The broad range of viscosity values stems from the gradual loss of water from RBCs over their 120-day lifespan. Our findings indicate that older RBCs exhibit more than twice the cytosol viscosity of younger cells, a critical factor for future theoretical studies of physiological conditions.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"73 6 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144646018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycine receptor and release site organization impacts the kinetics of glycinergic synapse currents.","authors":"Ronel Elbaz, Yarden Levinsky, Limor Freifeld","doi":"10.1016/j.bpj.2025.06.007","DOIUrl":"10.1016/j.bpj.2025.06.007","url":null,"abstract":"<p><p>Glycinergic synapses are the most abundant inhibitory synapses in the brainstem and spinal cord and are important for mediating rhythmic behaviors, such as locomotion and breathing. These synapses present significant variability in sizes and the intrasynaptic nanostructural organization of postsynaptic receptor clusters and presynaptic transmitter release sites. For example, in some cell types glycinergic synapses are comprised of multiple large receptor clusters located at the synapse periphery. Moreover, it has been shown that glycinergic synapses, similarly to other excitatory and inhibitory synapses, can be organized in transsynaptic nanocolumns comprised of presynaptic transmitter release sites precisely aligned opposed to dense postsynaptic receptor nanoclusters. However, while previous work has explored the functional roles of analogous specializations at other synapse types, the functional roles of these structural features have not been explored in glycinergic synapses. Here, we use a Monte Carlo simulation framework (MCell/Blender) to capture synapse structure-function relations in glycinergic synapses. In particular, we model glycinergic synapse currents in synapses containing peripheral receptors and ones comprised of transsynaptic nanocolumns, and compare these with currents in more simply organized synapses. Thus, we discover that the organization of receptors and release sites in glycinergic synapses strongly affects current kinetics, with smaller effects on amplitudes. Specifically, peripheral positioning of receptors makes synaptic currents decay rapidly, while forming transsynaptic nanocolumns gives rise to more sustained currents, where the decay rate decreases with receptor density. Put together, this implies that the formation of transsynaptic nanocolumns is required for large glycinergic synapses with peripherally located receptors to present sustained currents. These effects on the kinetics of glycinergic inhibitory synapse currents are expected, in turn, to shape how excitatory inputs inhibited by these synapses would be integrated by the cell.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"2327-2338"},"PeriodicalIF":3.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144282249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delayed phosphate release can highly improve energy efficiency of muscle contraction.","authors":"Jiaxiang Xu, Jiangke Tao, Bin Chen","doi":"10.1016/j.bpj.2025.06.002","DOIUrl":"10.1016/j.bpj.2025.06.002","url":null,"abstract":"<p><p>While the power stroke of myosin and the release of inorganic phosphate (Pi) play crucial roles in transforming ATP's chemical energy into mechanical work across diverse biological systems, the exact temporal relationship between these events continues to be intensely debated. In this study, from a functional perspective, we computationally investigate the impact of Pi release kinetics during the power stroke on muscle contraction dynamics. By implementing a mechanics model of the sarcomere unit that comprehensively incorporates the chemomechanical cycle of individual myosin molecules, we successfully replicate a broad range of experimental observations through parameter variation. Our simulation results reveal that delayed Pi release can significantly enhance energy efficiency during muscle contraction. This work suggests 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.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"2303-2316"},"PeriodicalIF":3.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macroscale optimal size of ICM vesicles regulated by quantum design principle in LH2 structure.","authors":"Ying Zhang, Qianjin Chu, Luchao Du, Yugui Yao, Hailong Chen, Peng Wang, Jianping Zhang, Mingqing Chen, Lingfeng Peng, Yuxiang Weng","doi":"10.1016/j.bpj.2025.06.004","DOIUrl":"10.1016/j.bpj.2025.06.004","url":null,"abstract":"<p><p>The photosynthetic bacterial light-harvesting antenna complex 2 (LH2), consisting of ring-like bacteriochlorophylls aggregates, constitutes an optimal excitonic structure for efficient energy transfer. Any distortion from this structure would cause efficiency losses. When adapted to low-light growing conditions, LH2-embedded membranes form vesicles to enhance light capture, albeit at the expense of curvature-induced LH2 deformation. Therefore, evolution should optimize vesicle sizes for overall light utilization efficiency. To unveil this optimization strategy, LH2 was assembled onto silica nanoparticles of a wide size region to simulate LH2 deformation, which was characterized by the B850 lifetime both theoretically and experimentally. We found that LH2 was undeformed only within the size range of 50-80 nm, akin to vesicle sizes observed in bacteria, suggesting that vesicle size optimization follows the LH2 structural design principle.</p>","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"2317-2326"},"PeriodicalIF":3.2,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two modes in the absolute velocity statistics in cautious walks of laboratory rodents.","authors":"I S Midzyanovskaya,A A Rebik,O S Idzhilova,F S Smyk,V V Strelkov,N L Komarova,O A Chichigina","doi":"10.1016/j.bpj.2025.07.010","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.07.010","url":null,"abstract":"We have analyzed a large number of rodent tracks in open-field tests, in order to elucidate the statistics of their velocities. We found that the probability distribution of the absolute velocity of individual rodents can be approximated by a superposition of two Rayleigh distributions, with distinct characteristic velocities v1 and v2 with v1<v2; this is in contrast to the single Rayleigh distribution for the speed of a Brownian particle executing 2D random motion. We propose that the part of the distribution near the larger speed, v2, characterizes rodents' progressions in space, while the part near v1 describes other types of motion, such as lingering and body micromovements. We observed that the animals switched randomly between these two modes. Since the existence of the modes is observed both in pre-weaned, blind pups and in older animals, it cannot be ascribed to foraging, but rather reflects risk assessment and proactive inhibition. We called such motion \"cautious walks\". Statistical analysis of the data further revealed a biphasic decline in the absolute velocity auto-correlation function, with two characteristic times, τs<τl, where τs characterizes the width of absolute velocity peaks, and τl is associated with the timing of the switches between progression and lingering. To describe the motion, we propose a stochastic model whose 2D Langevin-like equation has a damping coefficient that switches between two values, representing mode switching in rodent locomotion. A mechanistic analogy of rodent cautious walks is a Brownian particle that randomly switches its mass between a lighter weight and a heavier weight. Techniques developed here may be applicable for locomotion studies in a wide variety of contexts, as long as tracking data of sufficient resolution are available.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"2 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}