Biophysical journal最新文献_第7页

Microscopic Insight into HIV Fusion Peptide-Mediated Dehydration and Packing Regulation in Membranes. HIV融合肽介导的脱水和膜内包装调控的显微观察。

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-06-23 DOI: 10.1016/j.bpj.2025.06.023

Shovon Swarnakar,Anurag Chaudhury,Maximilian W A Skoda,Hirak Chakraborty,Jaydeep K Basu

{"title":"Microscopic Insight into HIV Fusion Peptide-Mediated Dehydration and Packing Regulation in Membranes.","authors":"Shovon Swarnakar,Anurag Chaudhury,Maximilian W A Skoda,Hirak Chakraborty,Jaydeep K Basu","doi":"10.1016/j.bpj.2025.06.023","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.06.023","url":null,"abstract":"Human immunodeficiency virus (HIV) infection is believed to occur through the entry of virion into mammalian cells engineered by the interaction of its fusion peptide in particular gp41 with the plasma membranes. Despite having a significant understanding of the biochemical pathways of HIV infection a viable remedy is yet to be achieved. This necessitates the evaluation of peptide-induced microscopic biophysical changes of the host membrane that support viral entry. In this report, we present the first detailed microscopic insights into the mechanisms of gp41-mediated host membrane dehydration and packing regulation, obtained through the combined use of neutron reflectivity and fluorescence microscopy, which together provide high-resolution structural information. We observe that the highest gp41 activity occurs in phase-separated membranes with the lowest compression modulus and headgroup ordering. The introduction of charged lipids coupled with phase homogenization leads to a significant reduction of gp41 mediated dehydration and packing modulation despite reduced headgroup ordering in such membranes. Interestingly maximum fusion peptide penetration occurs in the charged membranes suggesting a very subtle interplay of membrane composition and peptide penetration and localization requirements which determine the activity of HIV fusion peptide which is likely to be of great significance for their fusogenicity. We suggest that our study and its outcomes could also be relevant for other fusogenic enveloped viruses and hence could have far-reaching implications for developing remedial action not just against HIV but other similar enveloped viruses.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"36 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478788","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

Structural mapping of patient-associated KCNMA1 gene variants 患者相关KCNMA1基因变异的结构定位

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-06-21 DOI: 10.1016/j.bpj.2025.06.012

Hans J. Moldenhauer, Kelly Tammen, Andrea L. Meredith

引用次数: 0

Recent Advances in Machine Learning and Coarse-Grained Potentials for Biomolecular Simulations and Their Applications 生物分子模拟中机器学习和粗粒度电位的最新进展及其应用

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-06-20 DOI: 10.1016/j.bpj.2025.06.019

Adolfo B. Poma, Alejandra Hinostroza Caldas, Luis F. Cofas-Vargas, Michael S. Jones, Andrew L. Ferguson, Leonardo Medrano Sandonas

{"title":"Recent Advances in Machine Learning and Coarse-Grained Potentials for Biomolecular Simulations and Their Applications","authors":"Adolfo B. Poma, Alejandra Hinostroza Caldas, Luis F. Cofas-Vargas, Michael S. Jones, Andrew L. Ferguson, Leonardo Medrano Sandonas","doi":"10.1016/j.bpj.2025.06.019","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.06.019","url":null,"abstract":"Biomolecular simulations played a crucial role in advancing our understanding of the complex dynamics in biological systems with applications ranging from drug discovery to the molecular characterization of virus-host interactions. Despite their success, biomolecular simulations face inherent challenges due to the multiscale nature of biological processes, which involve intricate interactions across a wide range of length- and timescales. All-atom (AA) molecular dynamics provides detailed insights at atomistic resolution, yet it remains limited by computational constraints, capturing only short timescales and small conformational changes. In contrast, coarse-grained (CG) models extend simulations to biologically relevant time and length scales by reducing molecular complexity. However, CG models sacrifice atomic-level accuracy, making the parameterization of reliable and transferable potentials a persistent challenge. This review discusses recent advancements in machine learning (ML)-driven biomolecular simulations, including the development of ML potentials with quantum-mechanical accuracy, ML-assisted backmapping strategies from CG to AA resolutions, and widely used CG potentials. By integrating ML and CG approaches, researchers can enhance simulation accuracy while extending time and length scales, overcoming key limitations in the study of biomolecular systems.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"14 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335449","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

miRNA-548t-3p-mediated downregulation of lamin A/C impairs nuclear mechanosensitivity and focal adhesion dynamics mirna -548t-3p介导的层粘连蛋白A/C下调会损害核机械敏感性和黏附动力学

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-06-19 DOI: 10.1016/j.bpj.2025.06.022

Dahee Lee, Jungsoo Suh, Yoonkwan Jang, Myungeun Suk, Tae-Jin Kim

{"title":"miRNA-548t-3p-mediated downregulation of lamin A/C impairs nuclear mechanosensitivity and focal adhesion dynamics","authors":"Dahee Lee, Jungsoo Suh, Yoonkwan Jang, Myungeun Suk, Tae-Jin Kim","doi":"10.1016/j.bpj.2025.06.022","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.06.022","url":null,"abstract":"Lamin proteins are essential structural elements of the nuclear envelope, critically involved in maintaining nuclear shape and mechanical stability. Lamin A/C, specifically, acts as a mechanotransducer that senses extracellular mechanical cues and transmits them into intracellular biochemical signals, thereby influencing cell adhesion, motility, and differentiation. Although microRNAs (miRNAs) have emerged as key regulators of cellular mechanotransduction pathways, the precise roles of miRNAs in modulating lamin A/C at the single-cell level have remained poorly understood. Here, we utilized advanced fluorescence resonance energy transfer (FRET)-based biosensors and traction force microscopy to elucidate the impact of miRNA-548t-3p-induced lamin A/C downregulation on nuclear mechanical properties in single cells. Our findings demonstrate that miRNA-548t-3p specifically reduces lamin A/C levels, resulting in decreased nuclear tension and compromised focal adhesion dynamics. Furthermore, miRNA-548t-3p significantly diminishes the ability of cells to sense and respond to variations in extracellular matrix stiffness, leading to reduced cellular traction forces. These results underscore the pivotal role of lamin A/C in cellular mechanosensitivity and highlight miRNA-548t-3p as a critical modulator of nuclear mechanotransduction and mechanical homeostasis at the single-cell scale. This study provides new insights into the complex interplay between miRNAs, nuclear mechanics, and cell-environment interactions, suggesting potential avenues for therapeutic intervention in diseases associated with disrupted mechanotransduction.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"146 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335450","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

Denaturation of firefly luciferase at heat shock temperatures captured in silico 在硅捕获的热冲击温度下萤火虫荧光素酶的变性

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-06-19 DOI: 10.1016/j.bpj.2025.06.021

Vishal D. Lashkari, Piotr E. Marszalek

{"title":"Denaturation of firefly luciferase at heat shock temperatures captured in silico","authors":"Vishal D. Lashkari, Piotr E. Marszalek","doi":"10.1016/j.bpj.2025.06.021","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.06.021","url":null,"abstract":"Firefly luciferase (Fluc) is a bioluminescent protein that is widely used in cell and molecular biology research. Specifically, it is a gold standard substrate in chaperone protein studies because its bioluminescence decrease and recovery are related to Fluc misfolding and chaperone-assisted refolding, respectively. Fluc is moderately stable at room temperature but quickly loses bioluminescent activity at elevated temperatures as a stable, misfolded conformation is induced which persists upon cooling Fluc to room temperature. The heat shock protein 70 chaperone system can revert such structural changes, restoring bioluminescent activity. While thermal denaturation of Fluc is often used in chaperone-assisted refolding reactions, little is known about the specific structural alterations that occur in Fluc at heat shock temperatures. In this study, we use comprehensive all-atom molecular dynamics simulations to investigate the structural dynamics of Fluc at room (∼25 °C) and heat shock temperatures (∼42 °C). We conduct simulations totaling over 100 μs across replicates which allows a misfolded equilibrium to be approached. We find that at heat shock temperatures, Fluc undergoes subtle but long-lasting and reproducible conformational changes, namely the complete and irreversible denaturation of the α-helix at residues 405-411. We show the potential for this discrete change to inhibit Fluc bioluminescent activity. This consistent α-helix denaturation, along with other small secondary structure changes outlined in this work, are potential targets for chaperone systems known to restore Fluc activity after thermal denaturation. Therefore, our results inform a refined mechanism for chaperone-assisted refolding in which chaperone proteins may restore protein function by fixing localized structural perturbations as opposed to refolding an entirely denatured polypeptide chain.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"17 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335451","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

Mechanical memory of excitable cells induced by mechanosensitive channel inactivation. 机械敏感通道失活诱导可兴奋细胞的机械记忆。

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-06-18 DOI: 10.1016/j.bpj.2025.06.014

Jinjiang Xie,Fangtao Mao,Yuehua Yang,Hongyuan Jiang

{"title":"Mechanical memory of excitable cells induced by mechanosensitive channel inactivation.","authors":"Jinjiang Xie,Fangtao Mao,Yuehua Yang,Hongyuan Jiang","doi":"10.1016/j.bpj.2025.06.014","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.06.014","url":null,"abstract":"Recent experiments have unveiled a fascinating phenomenon: excitable cells exhibit mechanical memory, whereby their present excitation behaviours strongly depend on their past mechanical experiences. However, the underlying mechanism of this phenomenon remains elusive. Here, we introduce an electromechanical framework that integrates mechanical cell deformation, state transformations of mechanosensitive (MS) channels (such as Piezo channels), and transmembrane ion fluxes. We reveal that MS channel inactivation yields a history-dependent excitation dynamics, characterized by a progressive decline in subsequent activated currents with increasing amplitude, speed, and duration of prior mechanical stimuli. Moreover, MS channel inactivation in preceding stimulation results in a refractory period during which cells cannot elicit new action potentials upon subsequent mechanical stimuli. Finally, we show that cells can adapt to preceding mechanical stimulation due to inactivation of MS channels, resulting in a higher activated threshold stimulation. Thus, MS channel inactivation favors the reduction of firing activities in response to prolonged and repeated mechanical stimuli (\"neural adaptation\"), which may protect neurons against over-activation and damage. We then conduct two virtual experiments to predict how changes in mechanical properties of neurons modify their excitation behaviours. These findings together emphasize a critical role of MS channel inactivation in governing the mechanical memory and neural adaptation of excitable cells, shedding new light on the intricate interplay between mechanical forces and cellular electrical responses.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"37 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144328681","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

Illuminating Rhodopsin Activation in Real Time. 实时照明视紫红质激活。

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-06-18 DOI: 10.1016/j.bpj.2025.06.018

Kota Katayama

引用次数: 0

In silico Identification of Substrate Binding Sites in Type-1A α-Synuclein Amyloids. 1a型α-突触核蛋白淀粉样蛋白底物结合位点的计算机鉴定。

IF 3.4 3区生物学

Biophysical journal Pub Date : 2025-06-18 DOI: 10.1016/j.bpj.2025.06.017

Shraddha Parate,Fiamma Buratti,Leif A Eriksson,Pernilla Wittung-Stafshede

{"title":"In silico Identification of Substrate Binding Sites in Type-1A α-Synuclein Amyloids.","authors":"Shraddha Parate,Fiamma Buratti,Leif A Eriksson,Pernilla Wittung-Stafshede","doi":"10.1016/j.bpj.2025.06.017","DOIUrl":"https://doi.org/10.1016/j.bpj.2025.06.017","url":null,"abstract":"Pathological amyloids associated with Parkinson's and Alzheimer's diseases have been shown to catalyze chemical reactions in vitro. To elucidate how small-molecule substrates interact with cross-β amyloid structures, we here employ computational approaches to investigate α-synuclein amyloid fibrils of the type-1A fold. Our initial binding pocket prediction analysis identified three distinct substrate-binding sites per protofilament, yielding a total of six sites in the dimeric type-1A amyloid structure. Molecular docking of the model phosphoester substrate para-nitrophenyl phosphate (pNPP), previously shown to be dephosphorylated by α-synuclein amyloids in vitro, was performed on the three identified sites. Docking was validated by molecular dynamics (MD) simulations for a period of 100 ns. The results revealed a pronounced preference for a single binding site (termed Site 2), as pNPP migrated to this region when primarily placed at the other two sites. Site 2 is located near the interface between the two protofilaments in a cavity enriched with lysine residues and histidine-50. Binding site analysis suggests stable, yet dynamic, interactions between pNPP and these residues in the α-synuclein amyloid fibril. Our work provides molecular-mechanistic details of the interaction between a small-molecule substrate and one α-synuclein amyloid polymorph. This framework may be extended to other reactive substrates and amyloid polymorphs.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":"15 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144328680","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

Dendritic synaptic integration modes under in vivo-like states. 活体状态下树突突触整合模式。

IF 3.2 3区生物学

Biophysical journal Pub Date : 2025-06-17 Epub Date: 2025-04-30 DOI: 10.1016/j.bpj.2025.04.028

Cesar C Ceballos, Rodrigo F O Pena

{"title":"Dendritic synaptic integration modes under in vivo-like states.","authors":"Cesar C Ceballos, Rodrigo F O Pena","doi":"10.1016/j.bpj.2025.04.028","DOIUrl":"10.1016/j.bpj.2025.04.028","url":null,"abstract":"The neural code remains undiscovered and understanding synaptic input integration under in vivo-like conditions is just the initial step toward unraveling it. Synaptic signals generate fast dendritic spikes through two main modes of temporal summation: coincidence detection and integration. In coincidence detection, dendrites fire only when multiple incoming signals arrive in rapid succession, whereas integration involves summation of postsynaptic potentials over longer periods with minimal membrane leakage. This process is influenced by ionic properties, especially as the membrane potential approaches the firing threshold, where inactivating currents play a critical role. However, the modulation of temporal summation by these currents under in vivo-like conditions has not been thoroughly studied. In our research, we used computer simulations of a single dendritic branch to investigate how three inactivating currents-A-type potassium, T-type calcium, and transient sodium-affect temporal summation. We found that calcium and sodium currents promote integrative behavior in dendrites, while potassium currents enhance their ability to act as coincidence detectors. By adjusting the levels of these currents in dendrites, neurons can flexibly switch between integration and coincidence detection modes, providing them with a versatile mechanism for complex tasks such as multiplexing. This flexibility could be key to understanding how neural circuits process information in real time.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"1979-1994"},"PeriodicalIF":3.2,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dynamic fluid layer around immotile yeast colonies mediates the spread of bacteria. 静止酵母菌菌落周围的动态流体层介导细菌的传播。

IF 3.2 3区生物学

Biophysical journal Pub Date : 2025-06-17 Epub Date: 2025-06-04 DOI: 10.1016/j.bpj.2025.04.022

Divakar Badal, Aloke Kumar, Varsha Singh, Danny Raj M

{"title":"Dynamic fluid layer around immotile yeast colonies mediates the spread of bacteria.","authors":"Divakar Badal, Aloke Kumar, Varsha Singh, Danny Raj M","doi":"10.1016/j.bpj.2025.04.022","DOIUrl":"10.1016/j.bpj.2025.04.022","url":null,"abstract":"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. This enhancement is not a result of chemical signaling but due to the formation of a fluid layer around the yeast cells, which locally allows the flagellated bacteria to swim. Proliferation of yeast changes this fluid landscape around it and leads to the dynamic spread of bacteria. Factors such as the growth rate ratios and the seeding composition of the microorganisms determine the optimal spread of the bacteria. Physical factors such as these may have a crucial role in the dynamics of polymicrobial communities in various ecological environments.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":"1918-1929"},"PeriodicalIF":3.2,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12256891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0