Biophysical journal最新文献

Predicting red blood cell transport and capillary hemodynamics in angiogenic and tumor vascular networks in silico. 预测血管生成和肿瘤血管网络中的红细胞运输和毛细血管血流动力学。

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-10-06 DOI: 10.1016/j.bpj.2025.10.004

Abhay Mohan,Prosenjit Bagchi

{"title":"Predicting red blood cell transport and capillary hemodynamics in angiogenic and tumor vascular networks in silico.","authors":"Abhay Mohan,Prosenjit Bagchi","doi":"10.1016/j.bpj.2025.10.004","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.10.004","url":null,"abstract":"Blood flow through capillary vessels in cancerous tissue plays a crucial role in disease progression and treatment. Unlike the microvasculature in healthy tissue, which is hierarchically well-organized, a cancerous tissue is characterized by chaotic organization. A detailed quantification of blood cell transport and capillary hemodynamics in tumor microvasculature is lacking. Specifically, the relationship between tumor vascular geometric abnormalities, the dynamics of flowing blood cells, and the resulting blood flow anomalies at the vasculature scale is unknown. To fill this knowledge gap, we utilize a high-fidelity computational model of flow of a deformable red blood cell (RBC) suspension through angiogenic and tumor microvasculatures in silico built from in vivo/ex vivo images. We provide detailed quantitative distinctions between the healthy, angiogenic, and tumor microcirculation by predicting hemodynamic parameters that are difficult to experimentally measure but physiologically significant. These include the shape and dynamics of individual RBCs, the Fahraeus effect, blood viscosity, wall shear stress, and a 3D mapping of the RBC-depleted region near the vascular surface. This study opens a new avenue for studying tumor microcirculation using high-fidelity computational modeling in revealing novel microcirculatory phenomena in silico.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"74 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240873","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}

引用次数: 0

Stochastic Kinetics of mRNA Molecules in a General Transcription Model. 一般转录模型中mRNA分子的随机动力学。

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-10-03 DOI: 10.1016/j.bpj.2025.09.045

Yuntao Lu,Yunxin Zhang

{"title":"Stochastic Kinetics of mRNA Molecules in a General Transcription Model.","authors":"Yuntao Lu,Yunxin Zhang","doi":"10.1016/j.bpj.2025.09.045","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.09.045","url":null,"abstract":"Stochastic modeling of transcription is a classic yet long-standing problem in theoretical biophysics. The lack of unified results and a computationally efficient approach for a general, fine-grained transcription model has confined relevant research to some over-simplified special cases like the Telegraph model. This article establishes a general, unified and computationally efficient framework for studying stochastic transcription kinetics. We consider a chemical reaction model of transcription and construct the time-dependent solution to the corresponding chemical master equation. A well-known matrix-form expression for steady-state binomial moments is recovered by calculating the temporal limit of the time-dependent dynamics. Two novel inequalities for binomial moments and the probability mass function are derived using techniques from functional analysis. It follows that the distribution of mRNA counts is upper-bounded by a constant multiple of Poisson distribution, thus mathematically proving the main statement of the Heavy-Tailed Law. Additionally, the standard binomial moment method is analyzed from a numerical perspective, where truncation error is estimated using our inequalities. Compared with some widely-used numerical methods, a key advantage of this result is the significantly lower computational complexity.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"78 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226660","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}

引用次数: 0

Helical Sensors of Membrane Saturation: Changes in Orientation and Curvature Preference. 膜饱和的螺旋传感器：取向和曲率偏好的变化。

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-10-03 DOI: 10.1016/j.bpj.2025.09.042

Sushmita Pal,Peter Pajtinka,Matti Javanainen,Robert Vácha

{"title":"Helical Sensors of Membrane Saturation: Changes in Orientation and Curvature Preference.","authors":"Sushmita Pal,Peter Pajtinka,Matti Javanainen,Robert Vácha","doi":"10.1016/j.bpj.2025.09.042","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.09.042","url":null,"abstract":"The degree of unsaturation in lipids, which refers to the number of double bonds in their acyl chains, influences properties such as fluidity and lipid packing. However, it is not well understood how the unsaturation affects the ability of peptides to sense membrane curvature. In our study, we compared membranes with varying levels of unsaturation: mono-unsaturated POPC; bis-unsaturated DOPC; and poly-unsaturated PAPC. We investigated how these membranes interact with peptides of varying hydrophobicity. Using coarse-grained molecular dynamics simulations, we found that increasing unsaturation leads to deeper peptide insertion into the lipid bilayer, which correlates with a shift in curvature preference toward more negative values. We demonstrate that specific peptides preferentially localize on the positively curved regions in saturated membranes but shift preference to negatively curved regions in unsaturated membranes, thereby functioning as sensors of membrane unsaturation. In addition, polyunsaturated lipids facilitate the reorientation of peptides from a membrane-adsorbed state to a transmembrane state. These findings may play a role in biological processes such as vesicle formation, membrane fusion, and protein sorting, and highlight the adaptability of peptides to different lipid compositions in membranes.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"86 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226657","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}

引用次数: 0

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-10-03 DOI: 10.1016/j.bpj.2025.09.049

Javor K Novev,Sebastian E Ahnert

{"title":"Disease-related miRNA mutations are associated with mature miRNA secondary structure changes.","authors":"Javor K Novev,Sebastian E Ahnert","doi":"10.1016/j.bpj.2025.09.049","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.09.049","url":null,"abstract":"MicroRNAs (miRNAs) are ubiquitous short RNAs regulating gene expression in many organisms, including humans. How the secondary structure (SS) of a mature miRNA affects its regulatory function remains an open question. Here we investigate this question through computational SS predictions of miRNA point mutants. We explore the mutational neighborhoods of miRNAs with association to human diseases, including cancer. We focus on possible SS changes independent of target-site complementarity, by leaving the seed region unchanged. We formulate metrics of the SS differences between such mutants and their wild types (WTs), and test whether disease-associated mutations tend to differ from others in terms of these metrics by comparing our results with the miRNASNP-v3 database. We find that disease-related mutants tend to have a higher probability of being fully unfolded than their WT; this and other SS-related measures are statistically significant at the database level. This is confirmed when we restrict the analysis to the better-validated miRNAs encoded by genes that appear in the manually curated MiRGeneDB database. With the same approach, we identify a subset of individual miRNAs for which SS changes are most likely to be related to disease. These are hsa-miR-1269b, hsa-miR-4537, hsa-miR-4477b, hsa-miR-4641, and hsa-miR-6821-3p; when focussing on the higher-confidence MiRGeneDB miRNAs, we find that hsa-miR-485-5p and hsa-miR-1908-3p are the ones for which SS changes are most likely to be linked to disease. In addition, we show that there are pairs of known miRNA WTs differing only by disease-related point mutations outside the seed region and exhibit very different SS. These pairs include hsa-miR-1269a-hsa-miR-1269b, and hsa-miR-3689a-3p-hsa-miR-3689b-3p.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"97 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145215798","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}

引用次数: 0

The influence of proline on surface interactions in aqueous solutions. 脯氨酸对水溶液中表面相互作用的影响。

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-10-01 DOI: 10.1016/j.bpj.2025.09.043

Kieran J Agg,James E Hallett,Susan Perkin

引用次数: 0

Effectiveness of outer hair cells as cochlear amplifier: In simple model systems. 外毛细胞作为耳蜗放大器的有效性：在简单模型系统中。

IF 3.1 3区生物学

Biophysical journal Pub Date : 2025-10-01 DOI: 10.1016/j.bpj.2025.09.039

Kuni H Iwasa

引用次数: 0

Long-read nucleosome mapping of single chromatin fibers using DNA methylation and Nanopore sequencing. 利用DNA甲基化和纳米孔测序对单个染色质纤维进行长读核小体定位。

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-10-01 DOI: 10.1016/j.bpj.2025.09.048

Gert-Jan Kuijntjes,Tineke L Lenstra,John van Noort

{"title":"Long-read nucleosome mapping of single chromatin fibers using DNA methylation and Nanopore sequencing.","authors":"Gert-Jan Kuijntjes,Tineke L Lenstra,John van Noort","doi":"10.1016/j.bpj.2025.09.048","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.09.048","url":null,"abstract":"DNA elements such as genes and their regulatory regions must become accessible for protein binding when transcription is activated, which requires reorganization of the nucleosomes that fold the DNA into chromatin fibers. MNase-seq has been instrumental in uncovering the interplay between gene activity and chromatin organization by mapping the average nucleosome occupancy in populations of cells. However, better mechanistic understanding can be obtained from assays that can map nucleosomes along long strands of DNA at single-molecule resolution and without averaging. Here, we show that the combination of DNA methylation, long-read Nanopore sequencing and a novel nucleosome mapping algorithm based on statistical physics results in precise nucleosome footprinting at the single-molecule level over DNA loci exceeding several 10s of kbp. Accurate nucleosome mapping was verified in vitro, using chromatin reconstituted on tandem arrays of nucleosome positioning elements. Genome-wide application on Saccharomyces cerevisiae grown in different transcriptional conditions revealed large heterogeneity of nucleosome distributions upon transcription activation of the model GAL locus. Moreover, neighboring repeats of the ribosomal transcript RDN1 featured long-range correlations in nucleosome occupancy that we attribute to differential transcriptional activity. This enhanced assay allows for both meta-occupancy analysis, as well as in-depth single-fiber comparisons of local chromatin aberrations in context of transcription, DNA repair and other processes, illustrating the added value of single-molecule nucleosome mapping using long-read sequencing compared to traditional population averaged maps.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"120 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209326","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}

引用次数: 0

Reduced Binding of Tau(210-240) to BIN1: Phosphate Charges Prefer n-Src/Distal Loops over RT-Src Loops. Tau（210-240）与BIN1的结合减少：磷酸盐电荷更喜欢n-Src/远端环而不是RT-Src环。

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-09-30 DOI: 10.1016/j.bpj.2025.09.037

Amina Gaffour,Michael Bakker,Krishnendu Bera,Jana Pavlíková Přecechtělová

{"title":"Reduced Binding of Tau(210-240) to BIN1: Phosphate Charges Prefer n-Src/Distal Loops over RT-Src Loops.","authors":"Amina Gaffour,Michael Bakker,Krishnendu Bera,Jana Pavlíková Přecechtělová","doi":"10.1016/j.bpj.2025.09.037","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.09.037","url":null,"abstract":"Within the disordered tangles of Tau is a proline-rich region (PRR) which is selectively targeted by the SH3 domain of BIN1, a known genetic factor for Alzheimer's disease, and may hold the key to understanding the disorder and treatment strategies. Hyperphosphorylation of Tau is known to disrupt complex formation, providing researchers with an excellent preventative or remediative targets. This work compiles an extensive (>60 μs) collection of all-atomistic molecular dynamics (MD) simulations of the Tau(210-240) fragment, representing the majority of the P2 subdomain of the PRR, benchmarking various forcefields, phosphorylations, and modifications against experimental NMR chemical shifts and spin-spin coupling for comparison. Additionally, several simulations of the binding complex analyzed for their binding energies by MMGBSA calculations and computational alanine scanning to pinpoint the exact residues involved, and the disruptions caused by the phosphate group. We noted that the additional charges decrease salt-bridges formed by positive residues in Tau, particularly on R221, and negative residues in BIN1 by up to 32%, and a strong preference in Tau, particularly in the latter half, for contact towards the distal and n-Src loops instead of residues in the RT-Src loop.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"42 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145203450","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}

引用次数: 0

Evaluating single-cell variability in proteasomal decay within Saccharomyces cerevisiae. 评价酿酒酵母蛋白酶体衰变中的单细胞变异性。

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-09-30 DOI: 10.1016/j.bpj.2025.09.041

Sukanya Das,Abhyudai Singh,Premal Shah

{"title":"Evaluating single-cell variability in proteasomal decay within Saccharomyces cerevisiae.","authors":"Sukanya Das,Abhyudai Singh,Premal Shah","doi":"10.1016/j.bpj.2025.09.041","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.09.041","url":null,"abstract":"Gene expression is a stochastic process that leads to variability in mRNA and protein abundances even within an isogenic population of cells grown in the same environment. This variation, often called gene-expression noise, has typically been attributed to transcriptional and translational processes while ignoring the contributions of protein decay variability across cells. Here we estimate the single-cell protein decay rates of two degron GFPs in Saccharomyces cerevisiae using time-lapse microscopy. We find substantial cell-to-cell variability in the decay rates of the degron GFPs. We evaluate cellular features that explain the variability in the proteasomal decay and find that the amount of 20s catalytic beta subunit of the proteasome marginally explains the observed variability in the degron GFP half-lives. We propose alternate hypotheses that might explain the observed variability in the decay of the two degron GFPs. Overall, our study highlights the importance of studying the kinetics of the decay process at single-cell resolution and that decay rates vary at the single-cell level, and that the decay process is stochastic. A complex model of decay dynamics must be included when modeling stochastic gene expression to estimate gene expression noise.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"69 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194786","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}

引用次数: 0

Milestone for the interpretation of muscle X-ray diffraction patterns. 肌肉x射线衍射图谱的里程碑。

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-09-30 DOI: 10.1016/j.bpj.2025.09.046

Anthony L Hessel

引用次数: 0