Physical biology最新文献

Stability analysis under intrinsic fluctuations: a second-moment perspective of gene regulatory networks. 内在波动下的稳定性分析：基因调控网络的第二时刻视角。

IF 1.6 4区生物学

Physical biology Pub Date : 2025-10-08 DOI: 10.1088/1478-3975/ae0b22

Manuel Eduardo Hernández-García, Mariana Gómez-Schiavon, Jorge Velázquez-Castro

{"title":"Stability analysis under intrinsic fluctuations: a second-moment perspective of gene regulatory networks.","authors":"Manuel Eduardo Hernández-García, Mariana Gómez-Schiavon, Jorge Velázquez-Castro","doi":"10.1088/1478-3975/ae0b22","DOIUrl":"10.1088/1478-3975/ae0b22","url":null,"abstract":"Gene regulatory networks with negative feedback play a crucial role in conferring robustness and evolutionary resilience to biological systems. However, the discrete nature of molecular components and probabilistic interactions in these networks are inherently subject to fluctuations, which pose challenges for stability analysis. Traditional analysis methods for stochastic systems, like the Langevin equation and the Fokker-Planck equation, are widely used. However, these methods primarily provide approximations of system behavior and may not be suitable for systems that exhibit non-mass-action kinetics, such as those described by Hill functions. In this study, we employed a second-moment approach to analyze the stability of a gene regulatory network with negative feedback under intrinsic fluctuations. By transforming the stochastic system into a set of ordinary differential equations for the mean concentration and second central moment, we performed a stability analysis similar to that used in deterministic models, where there are no fluctuations. Our results show that the incorporation of the second central moment introduces two additional negative eigenvalues, indicating that the system remains stable under intrinsic fluctuations. Furthermore, the stability of the second central moment suggests that the fluctuations do not induce instability in the system. The stationary values of the mean concentrations were found to be the same as those in the deterministic case, indicating that fluctuations did not influence stationary mean concentrations. This framework provides a practical and insightful method for analyzing the stability of stochastic systems and can be extended to other biochemical networks with regulatory feedback and intrinsic fluctuations through a framework of ordinary differential equations.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Probing Domain Interactions in a Large Multimeric Protein: Molecular Dynamics and Bioinformatic Analysis of Closed and Open States of RyR1. 探测大多聚体蛋白结构域相互作用：RyR1闭合和开放状态的分子动力学和生物信息学分析。

IF 1.6 4区生物学

Physical biology Pub Date : 2025-10-08 DOI: 10.1088/1478-3975/ae10f7

Panisak Boonamnaj, Panyakorn Taweechat, Pisit Lerttanakij, R B Pandey, Montserrat Samsó, Pornthep Sompornpisut

{"title":"Probing Domain Interactions in a Large Multimeric Protein: Molecular Dynamics and Bioinformatic Analysis of Closed and Open States of RyR1.","authors":"Panisak Boonamnaj, Panyakorn Taweechat, Pisit Lerttanakij, R B Pandey, Montserrat Samsó, Pornthep Sompornpisut","doi":"10.1088/1478-3975/ae10f7","DOIUrl":"https://doi.org/10.1088/1478-3975/ae10f7","url":null,"abstract":"The ryanodine receptor isoform-1 (RyR1) is a large intracellular calcium release channel essential for skeletal muscle contraction. While cryo-electron microscopy (cryo-EM) has revealed structural snapshots of RyR1 in closed and open states, the dynamic features associated with calcium-dependent gating remain incompletely understood. In this study, we integrated all-atom molecular dynamics (MD) simulations with domain-level bioinformatic analyses to characterize and compare the structural dynamics of RyR1 in its closed and open conformations. Our simulations revealed distinct structural differences, including domain flexibility patterns, solvent accessibility, and hydrogen bonding networks, between the closed and open states. The closed state exhibited more extensive inter-subunit contacts and stable hydrogen-bonding networks, supporting a compact architecture characterized by inter-subunit domain engagement and intra-subunit domain loosening. In contrast, the open state showed increased solvent exposure and reduced inter-subunit interactions, reflecting inter-subunit domain loosening coupled with intra-subunit domain engagement, particularly in regions connecting the cytoplasmic and pore-forming domains. The comparative approach provides structural perspectives on how calcium binding may contribute to RyR1's conformational organization relevant to gating function. Our findings highlight the utility of integrating MD simulations with domain-scale analyses to investigate large protein complexes and generate hypotheses for future experimental validation.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Hierarchical switching pattern in antigenic variation provides survival advantage for malaria parasites under variable host immunity. 抗原变异的层次转换模式为疟原虫在不同宿主免疫条件下的生存提供了优势。

IF 1.6 4区生物学

Physical biology Pub Date : 2025-10-07 DOI: 10.1088/1478-3975/ae1091

Gayathri Priya Iragavarapu, Varsha Hj, Shruthi Sridhar Vembar, Bhaswar Ghosh

{"title":"Hierarchical switching pattern in antigenic variation provides survival advantage for malaria parasites under variable host immunity.","authors":"Gayathri Priya Iragavarapu, Varsha Hj, Shruthi Sridhar Vembar, Bhaswar Ghosh","doi":"10.1088/1478-3975/ae1091","DOIUrl":"https://doi.org/10.1088/1478-3975/ae1091","url":null,"abstract":"The var multigene family, comprising approximately 60 members, encodes for variants of Plasmodium falciparum erythrocyte membrane protein or PfEMP1, a surface antigen which is crucial for parasite blood stage virulence. var genes are expressed in a mutually exclusive fashion and to evade immune detection, P. falciparum transcriptionally switches from one variant to another. It has been proposed that a biased hierarchical switching pattern optimizes the growth and survival of P. falciparum inside the human host. However, the need to establish a particular hierarchy is not well explored, since the growth advantage to the parasite remains the same even if gene identities are shuffled. Our theoretical analysis based on a Markov chain model, coupled with single cell RNA-seq data analysis, RT-qPCR and RNA-seq measurements, establishes a hierarchical var gene expression pattern underlying the biased switching pattern. Further, inclusion of host immune response in the model suggests that the observed switching hierarchy is beneficial when cells expressing different variants are cleared at variable rates by the immune response. For instance, PfEMP1 variants that are cleared more efficiently by the immune system are expressed stably and at a higher level in the population compared to variants that are cleared slowly by the immune system, with parasites quickly turning off the expression of the slowly cleared variant. Consistent with these findings, analysis of published experimental data showed that stable variants exhibit greater binding affinities to IgM. Taken together, our study provides a mechanistic basis for the hierarchical switching pattern of P. falciparum var genes observed during infection.&#xD.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Cyclic Constraint on the Protein-RNA/DNA Interaction. 蛋白质- rna /DNA相互作用的循环约束。

IF 1.6 4区生物学

Physical biology Pub Date : 2025-10-03 DOI: 10.1088/1478-3975/ae0f33

Hamze Mousavi, Ronak Emami

{"title":"Cyclic Constraint on the Protein-RNA/DNA Interaction.","authors":"Hamze Mousavi, Ronak Emami","doi":"10.1088/1478-3975/ae0f33","DOIUrl":"https://doi.org/10.1088/1478-3975/ae0f33","url":null,"abstract":"The engagement of protein and RNA/DNA is examined in three varied conformations of protein molecules and two different configurations of RNA/DNA, namely finite and cyclic. This analysis emphasizes density of states and band structures by making use of a tight-binding Hamiltonian in combination with Green's function techniques. At a steady temperature and a defined quantity of building blocks in the RNA and DNA strands, the spectral diagrams show flat energy curves for both RNA and DNA molecules, showcasing characteristics akin to those found in semiconductors. The key distinctions between the cyclic configuration and the finite case lie in the peak height and the arrangement of the peaks in the density of states, as well as the shifts in band positions. The coupling of protein molecules with the RNA and DNA models yields a reduction of the energy gap in the protein-RNA system and a progression from semiconductor properties to metallic ones in the protein-DNA structure. Furthermore, the role of temperature in determining the density of states leads to changes in the peak levels and their respective positions. It is expected that the coupling of protein and RNA/DNA will directly exert a straightforward influence on the electronic attributes of RNA/DNA, which differ among diverse protein structures, thus creating opportunities for newly conducted research with significant biological implications.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Fractal Measures as Predictors of Histopathological Complexity in Breast Carcinoma Mammograms. 分形测量作为乳腺癌乳房x光片组织病理复杂性的预测因子。

IF 1.6 4区生物学

Physical biology Pub Date : 2025-10-03 DOI: 10.1088/1478-3975/ae0f6e

Abhijeet Das, Ramray Bhat, Mohit Kumar Jolly

{"title":"Fractal Measures as Predictors of Histopathological Complexity in Breast Carcinoma Mammograms.","authors":"Abhijeet Das, Ramray Bhat, Mohit Kumar Jolly","doi":"10.1088/1478-3975/ae0f6e","DOIUrl":"https://doi.org/10.1088/1478-3975/ae0f6e","url":null,"abstract":"This study investigates the efficacy of fractal-based global texture features for distinguishing between malignant and normal mammograms and assessing their potential for molecular subtype differentiation. Digital mammograms were analyzed using standardized preprocessing techniques, and fractal measures were computed to capture complexity and connectivity properties within breast tissue structures. We introduced the succolarity reservoir as a novel parameter accounting for tissues' latent connectivity. Fractal dimension, multifractality strength, and succolarity reservoir were found to effectively characterize specific features of mammographic texture in contrast to lacunarity and Rényi dimensions; however, their incorporation into machine learning models yielded moderate discriminatory performance between categories. In addition, while succolarity reservoir exhibits conceptual potential for differentiating Luminal B from other molecular subtypes, its overall discriminative power remains limited. This proof-of-concept study underscores the exploratory potential of fractal-based texture analysis as a non-invasive biomarker in breast carcinoma diagnosis.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Mutually inhibiting teams of nodes: A predictive framework for structure-dynamics relationships in gene regulatory networks. 相互抑制的节点团队：基因调控网络中结构-动力学关系的预测框架。

IF 1.6 4区生物学

Physical biology Pub Date : 2025-10-02 DOI: 10.1088/1478-3975/ae0ef6

Sai Shyam Shyam, Nikhil Nandan, Vaibhav Anand, Mohit Kumar Jolly, Kishore Hari

{"title":"Mutually inhibiting teams of nodes: A predictive framework for structure-dynamics relationships in gene regulatory networks.","authors":"Sai Shyam Shyam, Nikhil Nandan, Vaibhav Anand, Mohit Kumar Jolly, Kishore Hari","doi":"10.1088/1478-3975/ae0ef6","DOIUrl":"https://doi.org/10.1088/1478-3975/ae0ef6","url":null,"abstract":"Phenotypic plasticity-the reversible switching of cell-states-is a central tenet of development, regeneration, and cancer progression. These transitions are governed by gene regulatory networks (GRNs), whose topological features strongly influence their dynamics. While toggle switches (mutually inhibitory feedback loops between two transcription factors) are a common motif observed for binary cell-fate decisions, GRNs across diverse contexts often exhibit a more general structure: two mutually inhibiting teams of nodes. Here, we investigate the teams of nodes as a potential topological design principle of GRNs. We first analyze GRNs from the Cell Collective database and introduce a metric, impurity, which quantifies the fraction of edges inconsistent with an idealized two-team architecture. Impurity correlates strongly with statistical properties of GRN phenotypic landscapes, highlighting its predictive value. To further probe this relationship, we simulate artificial two-team networks (TTNs) using both continuous (RACIPE) and discrete (Boolean) formalisms across varying impurity, density, and network size values. TTNs exhibit toggle-switch-like robustness under perturbations and enable accurate prediction of dynamical features such as inter-team correlations and steady-state entropy. Together, our findings establish the teams paradigm as a unifying principle linking GRN topology to dynamics, with broad implications for inferring coarse-grained network properties from high-throughput sequencing data.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Physical confinement and distance of migration cooperatively enhance chemotherapeutic resistance in migratory GBM cells. 物理限制和迁移距离共同增强了迁移性GBM细胞的化疗耐药性。

IF 1.6 4区生物学

Physical biology Pub Date : 2025-09-30 DOI: 10.1088/1478-3975/ae0dd7

Qionghua Shen, Adam Germain, Calvin Kong, Young-Tae Kim

{"title":"Physical confinement and distance of migration cooperatively enhance chemotherapeutic resistance in migratory GBM cells.","authors":"Qionghua Shen, Adam Germain, Calvin Kong, Young-Tae Kim","doi":"10.1088/1478-3975/ae0dd7","DOIUrl":"https://doi.org/10.1088/1478-3975/ae0dd7","url":null,"abstract":"Metastatic glioblastoma multiforme (GBM) is known for its dismal prognosis due to the dissemination of single cells throughout the brain parenchyma and along white matter tracts, resulting in heightened resistance to therapies. Understanding the intricate relationship between cell migration, physical confinement, and chemotherapeutic resistance in GBM is imperative for advancing treatment strategies. In this study, we employed G55, a representative migratory GBM cell line, to investigate this phenomenon. We generated three distinct cell populations: 1) cells migrating without confinement, assessed via the Scratch assay; 2) cells migrating short distance (10 μm) under confinement, examined through the Transwell assay; and 3) cells migrating long distances (> 100 μm) under confinement,studied usingthe Microchannel assay. Comparative analyses of protein expression profiles and chemotherapy sensitivity among these groups revealed that migration combined with physical confinement plays a pivotal role in augmenting chemotherapeutic resistance in interstitial invasive cancer cells. Moreover, we demonstrate the utility of the microchannel device, which facilitates controlled cell migration under physical confinement, as an effective in vitro tool for investigating metastatic cancer and associated treatment resistance. This study sheds light on the mechanisms underlying GBM progression and highlights potential avenues for therapeutic intervention.&#xD.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Active Gaussian network model: a non-equilibrium description of protein fluctuations and allosteric behavior. 主动高斯网络模型：蛋白质波动和变构行为的非平衡描述。

IF 1.6 4区生物学

Physical biology Pub Date : 2025-09-10 DOI: 10.1088/1478-3975/ae0081

Giulio Costantini, Lorenzo Caprini, Umberto Marini Bettolo Marconi, Fabio Cecconi

{"title":"Active Gaussian network model: a non-equilibrium description of protein fluctuations and allosteric behavior.","authors":"Giulio Costantini, Lorenzo Caprini, Umberto Marini Bettolo Marconi, Fabio Cecconi","doi":"10.1088/1478-3975/ae0081","DOIUrl":"10.1088/1478-3975/ae0081","url":null,"abstract":"Understanding the link between structure and function in proteins is fundamental in molecular biology and proteomics. A central question in this context is whether allostery-where the binding of a molecule at one site affects the activity of a distant site-emerges as a further manifestation of the intricate interplay between structure, function, and intrinsic dynamics. This study explores how allosteric regulation is modified when intrinsic protein dynamics operates under out-of-equilibrium conditions. To this purpose, we introduce a simple non-equilibrium model of protein dynamics, inspired by active matter systems, by generalizing the widely employed Gaussian network model to incorporate non-thermal effects. Our approach underscores the advantage of framing allostery as a causal process by using, as a benchmark system, the second PDZ domain of the human phosphatase human Protein Tyrosine Phosphatase 1E that mediates protein-protein interactions. We employ causal indicators, such as response functions and transfer entropy, to identify the network of PDZ2 residues through which the allosteric signal propagates across the protein structure. These indicators reveal specific regions that align well with experimental observations. Furthermore, our results suggest that deviations from purely thermal fluctuations can significantly influence allosteric communication by introducing distinct timescales and memory effects. This influence is particularly relevant when the allosteric response unfolds on timescales incompatible with relaxation to equilibrium. Accordingly, non-thermal fluctuations may become essential for accurately describing protein responses to ligand binding and developing a comprehensive understanding of allosteric regulation.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144965984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Phenotypic heterogeneity in temporally fluctuating environments. 在时间波动环境中的表型异质性。

IF 1.6 4区生物学

Physical biology Pub Date : 2025-08-14 DOI: 10.1088/1478-3975/adf790

Alexander P Browning, Sara Hamis

引用次数: 0

Regulation and functional roles revealed by clustering of microarray expression data ofEscherichia coligenes. 大肠杆菌基因微阵列表达数据聚类揭示的调控及其功能作用。

IF 1.6 4区生物学

Physical biology Pub Date : 2025-08-14 DOI: 10.1088/1478-3975/adf61a

Mishael Sánchez-Pérez, Humberto Peralta, M Cecilia Ishida-Guitierrez, Alberto Santos-Zavaleta, Irma Martínez-Flores, Faviola Tavares-Carreon, Cesaré Ovando-Vázquez

{"title":"Regulation and functional roles revealed by clustering of microarray expression data ofEscherichia coligenes.","authors":"Mishael Sánchez-Pérez, Humberto Peralta, M Cecilia Ishida-Guitierrez, Alberto Santos-Zavaleta, Irma Martínez-Flores, Faviola Tavares-Carreon, Cesaré Ovando-Vázquez","doi":"10.1088/1478-3975/adf61a","DOIUrl":"10.1088/1478-3975/adf61a","url":null,"abstract":"An enormous amount of gene expression data is currently available online in repositories for several organisms. Microarray data can be used to identify co-expressed genes that may be involved in the same biological process. Therefore, the analysis and interpretation of this information could help organize and understand the knowledge it contains, representing a major challenge in the post-genomic era. Here, we grouped genes ofEscherichia coliK-12 using expression data to infer meaningful transcriptional regulatory information. Our method assumes that co-expressed genes reflect functional units, as evidenced by their genetic structure, including gene arrangement, regulation, and participation in defined biological processes. These functionally linked clusters were validated with curated transcriptional regulatory information from RegulonDB. From 907 growth conditions, 420 clusters were formed involving 1674 genes. Clusters contained from 2 to 64 genes. We found that co-expressed genes participate in related metabolic pathways and share similar types of regulation (through transcription factors,σ-factors, allosteric regulation, or micro-RNA regulation). This study is helpful for identifying novel transcriptional regulatory interactions.","PeriodicalId":20207,"journal":{"name":"Physical biology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144754097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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