Biophysical journal最新文献

Cadherin Dynamics and Cortical Tension in Remodeling Cell-Cell Adhesion During EMT. EMT中重塑细胞黏附中的钙粘蛋白动力学和皮质张力。

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-05-05 DOI: 10.1016/j.bpj.2025.05.001

Hongyuan Zhu,Xiaoxi Liu,Jiayu Zhang,Guoqing Zhao,Jin Wang,Huan Zhang,Yan Liu,Hui Guo,Jin Yang,Zheng Wang,Tian Jian Lu,Feng Xu,Min Lin

{"title":"Cadherin Dynamics and Cortical Tension in Remodeling Cell-Cell Adhesion During EMT.","authors":"Hongyuan Zhu,Xiaoxi Liu,Jiayu Zhang,Guoqing Zhao,Jin Wang,Huan Zhang,Yan Liu,Hui Guo,Jin Yang,Zheng Wang,Tian Jian Lu,Feng Xu,Min Lin","doi":"10.1016/j.bpj.2025.05.001","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.05.001","url":null,"abstract":"Epithelial-to-mesenchymal transition (EMT), a key process in cancer metastasis and fibrosis, disrupts cellular adhesion by replacing epithelial E-cadherin with mesenchymal N-cadherin. While, how the shift from E-cadherin to N-cadherin impacts molecular-scale adhesion mechanics and cluster dynamics-and how these changes weaken adhesion under varying mechanical and environmental conditions-remains poorly understood, limiting our ability to target EMT-driven pathological adhesion dynamics. Here, we developed a unified Lattice-Clutch model to investigate cadherin clustering, cortical tension, and adhesion strength during EMT. Using atomic force microscopy (AFM) experiments, we measured the mechanical properties of single cadherin trans-bonds and cadherin-mediated cell-cell and cell-matrix adhesions across varying conditions. Our results demonstrate that N-cadherin trans-bonds are mechanically weaker than E-cadherin trans-bonds, leading to reduced adhesion strength during EMT. Computational modeling and experimental validation further revealed that EMT impairs cadherin clustering and cortical tension regulation, which collectively weaken both cell-cell and cell-matrix adhesions, particularly on stiff substrates. These findings highlight how EMT disrupts adhesion strength at multiple scales-from individual cadherin bonds to collective cluster dynamics. Our study elucidates how EMT-driven changes in cadherin type weaken adhesion strength and mechanotransduction, providing insights into cellular adhesion mechanics and potential therapeutic strategies for targeting EMT-associated diseases such as cancer metastasis and tissue remodeling.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"115 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914937","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

Modeling Riboswitches: The impact of Mg2+ ions concentration on the folding of the SAM-II riboswitch. 模拟核开关：Mg2+离子浓度对SAM-II核开关折叠的影响。

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-05-05 DOI: 10.1016/j.bpj.2025.04.032

Osama Alaidi

引用次数: 0

5'-tRNAHisGUG fragment: A preferred endogenous TLR7 Ligand with reverse sequence activation insights. 5'-tRNAHisGUG片段：具有反向序列激活见解的首选内源性TLR7配体

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-05-05 DOI: 10.1016/j.bpj.2025.04.027

Kiran Bharat Lokhande,Ashutosh Singh,Rajan Vyas,Shreya Joe,Shailendra Asthana,Kamlesh Pawar

{"title":"5'-tRNAHisGUG fragment: A preferred endogenous TLR7 Ligand with reverse sequence activation insights.","authors":"Kiran Bharat Lokhande,Ashutosh Singh,Rajan Vyas,Shreya Joe,Shailendra Asthana,Kamlesh Pawar","doi":"10.1016/j.bpj.2025.04.027","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.04.027","url":null,"abstract":"Toll-like receptor 7 (TLR7), a key member of the TLR family, plays a pivotal role in innate immunity, making it an attractive therapeutic target. However, current synthetic TLR7 agonists are often associated with significant toxicity, highlighting the need for safer, naturally occurring alternatives. Our recent research identified 5'-fragments of tRNAHisGUG (5'-HisGUG) and tRNAValCAC/AAC (5'-ValCAC/AAC) as potent, naturally occurring TLR7 activators. While endogenous RNAs like 5'-HisGUG are known to activate TLR7, the molecular details of their interaction remain unclear. To address this, we performed molecular dynamics simulations and MM/GBSA binding free energy analysis to investigate how these RNA fragments engage with TLR7 in comparison to synthetic agonists. Our results revealed that 5'-HisGUG, 5'-ValCAC/AAC, and reverse sequence (5'-HisGUG-Rev) exhibit strong binding affinities, with higher energetic favorability than synthetic agonists. The free energy fluctuations suggested that endogenous RNA ligands display greater conformational variability, possibly contributing to their activation potential. Notably, 5'-HisGUG-Rev effectively activated TLR7 and enhanced cytokine mRNA expression. Comparative analysis suggests that binding affinity alone does not directly predict activation, emphasizing the importance of both strong interaction and conformational flexibility in TLR7 activation. These findings position 5'-HisGUG as a promising natural TLR7 activator with potential therapeutic applications.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"39 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915205","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

Effect of RNA on the supramolecular architecture of α-synuclein fibrils. RNA对α-突触核蛋白原纤维超分子结构的影响。

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-05-05 DOI: 10.1016/j.bpj.2025.04.031

Antonia Intze,Maria Eleonora Temperini,Jakob Rupert,Raffaella Polito,Alexander Veber,Ljiljana Puskar,Ulrich Schade,Michele Ortolani,Elsa Zacco,Gian Gaetano Tartaglia,Valeria Giliberti

{"title":"Effect of RNA on the supramolecular architecture of α-synuclein fibrils.","authors":"Antonia Intze,Maria Eleonora Temperini,Jakob Rupert,Raffaella Polito,Alexander Veber,Ljiljana Puskar,Ulrich Schade,Michele Ortolani,Elsa Zacco,Gian Gaetano Tartaglia,Valeria Giliberti","doi":"10.1016/j.bpj.2025.04.031","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.04.031","url":null,"abstract":"Structural changes associated with protein aggregation are challenging to study, requiring the combination of experimental techniques providing insights at the molecular level across diverse scales, ranging from nanometers to microns. Understanding these changes is even more complex when aggregation occurs in the presence of molecular co-factors like nucleic acids and when the resulting aggregates are highly polymorphic. Infrared (IR) spectroscopy is a powerful tool for studying protein aggregates since it combines the label-free sensitivity to the cross-β architecture, an inherent feature of protein supramolecular aggregates, with the possibility to reach nanoscale sensitivity by leveraging atomic force microscopy-assisted (AFM-assisted) detection. Here, we present a combined approach that detects IR spectral markers of aggregation using various IR spectroscopy techniques, covering micro- to nano-scale ranges, to study the effect of RNA on the supramolecular architecture of α-synuclein amyloid aggregates. We show a clear impact of RNA consistent with enhanced inter-molecular forces, likely via a stronger hydrogen-bonded network stabilizing the cross-β architecture. AFM-assisted IR spectroscopy was crucial to assess that the more ordered the aggregates are, the stronger the structural impact of RNA. In addition, an RNA-induced reduction of the degree of polymorphism within the aggregate population is obtained.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"24 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915198","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

Low pH amplifies chemotaxis toward urea in Helicobacter pylori. 低pH值放大幽门螺杆菌对尿素的趋化性。

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-04-30 DOI: 10.1016/j.bpj.2025.04.026

Aakansha Shaji,Pravin Subrahmaniyan,Sayak Mukhopadhyay,Rachel Shin,Harini Santhoshkumar,Pushkar P Lele

{"title":"Low pH amplifies chemotaxis toward urea in Helicobacter pylori.","authors":"Aakansha Shaji,Pravin Subrahmaniyan,Sayak Mukhopadhyay,Rachel Shin,Harini Santhoshkumar,Pushkar P Lele","doi":"10.1016/j.bpj.2025.04.026","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.04.026","url":null,"abstract":"Helicobacter pylori infections increase the risk of non-cardia gastric adenocarcinoma, and chemotaxis toward metabolites such as urea plays a key role in modulating infection. Chemotaxis studies are more insightful in strains of H. pylori that are amenable to genetic modification, such as the G27 strain. However, motility in G27 cells can be inconsistent and varies with growth conditions, raising questions about its chemotaxis abilities. Here, we quantitatively compared motility and urea chemotaxis between the G27 strain and the highly motile PMSS1 strain. We observed that G27 cells swim ∼ 40% slower than the PMSS1 cells, likely because the former possessed one flagellum on average, whereas the latter had multiple flagella. Despite its slow swimming, G27 exhibited a strong chemotactic response to urea with optimal output under physiological temperature (37°C). Significantly, low pH conditions amplified the urea response, and comparisons of the experiments with a mathematical model suggested that low pH increases chemoreceptor sensitivity toward the metabolite. These results are consistent with the possibility that the harsh acidic environment of the stomach enhances migration toward urea, which the cells degrade to neutralize the local pH and facilitate their survival.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"54 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902892","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

Cholesterol Allosteric Modulation of the Oxytocin Receptor. 催产素受体的胆固醇变构调节。

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-04-29 DOI: 10.1016/j.bpj.2025.04.023

Brennica Marlow,Alexander Vogel,Georg Kuenze,Maik Pankonin,Franziska Reinhardt,Peter F Stadler,Peter W Hildebrand,Jens Meiler

{"title":"Cholesterol Allosteric Modulation of the Oxytocin Receptor.","authors":"Brennica Marlow,Alexander Vogel,Georg Kuenze,Maik Pankonin,Franziska Reinhardt,Peter F Stadler,Peter W Hildebrand,Jens Meiler","doi":"10.1016/j.bpj.2025.04.023","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.04.023","url":null,"abstract":"G-protein coupled receptors (GPCRs) are critical components in cellular signaling, mediating various physiological responses to external stimuli. Here, we investigate the intricate relationship between cholesterol and the oxytocin receptor (OXTR), focusing on the binding mechanisms and the allosteric crosstalk of bound cholesterol to the orthosteric ligand binding pocket. Utilizing molecular docking and molecular dynamics simulations, we identify cholesterol binding sites both on the agonist-bound and antagonist-bound state, which show differing distributions and residence times of the cholesterol molecules. Importantly, both methods converge on several key sites, demonstrating strong predictive overlap. Notably, one such site, and several sites detected by our MD approach, also coincides with electron density observed in an experimental cryo-EM map, providing orthogonal validation for computational predictions. Allosteric network analysis uncovers the distinct pathways through which cholesterol may affect ligand mediated receptor signaling, highlighting the significance of one site on the extracellular leaflet between TM4 and TM5, and two sites on the intracellular leaflet between TM2, TM3, and TM4 and between TM4 and TM5 in transmitting allosteric signals to the orthosteric pocket. These findings provide insights into the impact of cholesterol on OXTR function, emphasizing specific binding sites and signaling paths for further experimental exploration.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"90 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897410","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

Path sampling challenges in large biomolecular systems: RETIS and REPPTIS for ABL-imatinib kinetics 大生物分子系统的路径采样挑战：abl -伊马替尼动力学的RETIS和REPPTIS

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-04-23 DOI: 10.1016/j.bpj.2025.04.020

Wouter Vervust, Daniel T. Zhang, Enrico Riccardi, Titus S. van Erp, An Ghysels

{"title":"Path sampling challenges in large biomolecular systems: RETIS and REPPTIS for ABL-imatinib kinetics","authors":"Wouter Vervust, Daniel T. Zhang, Enrico Riccardi, Titus S. van Erp, An Ghysels","doi":"10.1016/j.bpj.2025.04.020","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.04.020","url":null,"abstract":"Predicting the kinetics of drug-protein interactions is crucial for understanding drug efficacy, particularly in personalized medicine, where protein mutations can significantly alter drug residence times. This study applies replica exchange transition interface sampling and its partial path variant to investigate the dissociation kinetics of imatinib from Abelson nonreceptor tyrosine kinase (ABL) and mutants relevant to chronic myeloid leukemia therapy. These path sampling methods offer a bias-free alternative to conventional approaches requiring qualitative predefined reaction coordinates. Nevertheless, the complex free energy landscape of ABL-imatinib dissociation presents significant challenges. Multiple metastable states and orthogonal barriers lead to parallel unbinding pathways, complicating convergence in transition interface sampling-based methods. Despite employing computational efficiency strategies such as asynchronous replica exchange, full convergence remained elusive. This work provides a critical assessment of path sampling in high-dimensional biological systems, discussing the need for enhanced initialization strategies, advanced Monte Carlo path generation moves, and machine learning-derived reaction coordinates to improve kinetic predictions of drug dissociation with minimal prior knowledge.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"22 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901810","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

Mechanistic basis for enhanced strigolactone sensitivity in KAI2 triple mutant KAI2三重突变体增强独角麦内酯敏感性的机制基础

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-04-23 DOI: 10.1016/j.bpj.2025.04.021

Briana L. Sobecks, Jiming Chen, Tanner J. Dean, Diwakar Shukla

{"title":"Mechanistic basis for enhanced strigolactone sensitivity in KAI2 triple mutant","authors":"Briana L. Sobecks, Jiming Chen, Tanner J. Dean, Diwakar Shukla","doi":"10.1016/j.bpj.2025.04.021","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.04.021","url":null,"abstract":"<ce:italic>Striga hermonthica</ce:italic> is a parasitic weed that destroys billions of dollars’ worth of staple crops every year. Its rapid proliferation stems from an enhanced ability to metabolize strigolactones (SLs), plant hormones that direct root branching and shoot growth. <ce:italic>Striga’s</ce:italic> SL receptor, <ce:italic>Sh</ce:italic>HTL7, bears more similarity to the staple crop karrikin receptor karrikin insensitive 2 (KAI2) than to SL receptor D14, though KAI2 variants in plants like <ce:italic>Arabidopsis thaliana</ce:italic> show minimal SL sensitivity. Recently, studies have indicated that a small number of point mutations to HTL7 residues can confer SL sensitivity to <ce:italic>At</ce:italic>KAI2. Here, we analyze both wild-type <ce:italic>At</ce:italic>KAI2 and SL-sensitive mutant Var64 through all-atom, long-timescale molecular dynamics simulations to determine the effects of these mutations on receptor function at a molecular level. We demonstrate that the mutations stabilize SL binding by about 2 kcal/mol. They also result in a doubling of the average pocket volume and eliminate the dependence of binding on certain pocket conformational arrangements. Although the probability of certain nonbinding SL-receptor interactions increases in the mutant compared with the wild-type, the rate of binding also increases by a factor of 10. All these changes account for the increased SL sensitivity in mutant KAI2 and suggest mechanisms for increasing the functionality of host crop SL receptors.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"139 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901809","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

"Poking cells: AI can help here too". “戳细胞：人工智能也能帮上忙”。

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-04-22 DOI: 10.1016/j.bpj.2025.04.019

Juanyong Li,Kristen Billiar

引用次数: 0

tRNA kinetics on the ribosome depends non-monotonically on intersubunit rotation. 核糖体上 tRNA 的动力学非单调地取决于亚基间的旋转。

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-04-18 DOI: 10.1016/j.bpj.2025.04.018

Sandra Byju,Paul C Whitford

{"title":"tRNA kinetics on the ribosome depends non-monotonically on intersubunit rotation.","authors":"Sandra Byju,Paul C Whitford","doi":"10.1016/j.bpj.2025.04.018","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.04.018","url":null,"abstract":"In order to translate messenger RNA into proteins, the ribosome must coordinate a wide range of conformational rearrangements. Some steps involve individual molecules, whereas others require synchronization of multiple collective motions. For example, the ribosomal \"small\" subunit (∼1 MDa) is known to undergo rotational motion (∼10°) that is correlated with large-scale displacements of tRNA molecules (∼50Å). While decades of biochemical, single-molecule and structural analysis have provided many insights into the timing of these motions, little is known about how these dynamical processes influence each other. To address this, we use molecular simulations to isolate specific interactions that allow tRNA kinetics to be controlled by subunit rotation. Specifically, we applied an all-atom structure-based model to simulate movement of tRNA between ribosomal binding sites (P/E hybrid formation). These calculations reveal a pronounced non-monotonic dependence of tRNA kinetics on subunit rotation, where the rate of P/E formation initially increases and then decreases as the subunit rotates. In addition, there a sharp increase in rate for low degrees of rotation, suggesting that adoption of P/E tRNA conformations may occur early in the rotation process. Together, these calculations demonstrate how molecular structure gives rise to an intricate relationship between these complex rearrangements.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"16 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143857293","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