Biophysical journal最新文献_第4页

Separation of sticker-spacer energetics governs the coalescence of metastable condensates.

IF 3.2 3区生物学

Biophysical journal Pub Date : 2024-12-15 DOI: 10.1016/j.bpj.2024.12.017

Aniruddha Chattaraj, Eugene I Shakhnovich

引用次数: 0

Role of cardiolipin in proton transmembrane flux and localization.

IF 3.2 3区生物学

Biophysical journal Pub Date : 2024-12-13 DOI: 10.1016/j.bpj.2024.12.015

Sylvain Domitin, Nicolas Puff, Fanny Pilot-Storck, Laurent Tiret, Frederic Joubert

{"title":"Role of cardiolipin in proton transmembrane flux and localization.","authors":"Sylvain Domitin, Nicolas Puff, Fanny Pilot-Storck, Laurent Tiret, Frederic Joubert","doi":"10.1016/j.bpj.2024.12.015","DOIUrl":"10.1016/j.bpj.2024.12.015","url":null,"abstract":"In eukaryotic cells, the phospholipid cardiolipin (CL) is a crucial component that influences the function and organization of the mitochondrial inner membrane. In this study, we examined its potential role in passive proton transmembrane flux using unilamellar vesicles composed of natural egg phosphatidylcholine (PC) alone or with the inclusion of 18 or 34 mol % CL. A membrane potential was induced by a potassium gradient, and oxonol VI dye was used to monitor membrane potential dissipation resulting from proton transmembrane efflux. Increasing the CL content led to a net increase in proton efflux, which was also dependent on the magnitude of the membrane potential. The same increase in proton efflux was measured in the presence of the equally negatively charged phosphatidylglycerol, indicating that the charge of CL plays a more important role than its structure in this mechanism. When varying the proton membrane permeability (pH) using the protonophore CCCP, we observed that unlike PC liposomes, where a small amount of CCCP was sufficient to achieve maximum flux, a significantly larger amount of protonophore was required in the presence of CL. Conversely, increasing the buffer capacity increased proton flux, indicating that proton availability, rather than membrane permeability, may be the limiting factor for proton leak. Our findings demonstrated that a higher proton content associated with the membrane was correlated with an increasing leak in the presence of CL. Additionally, smaller liposome diameters appeared to favor proton leak. Taken together, our results suggest that the presence of negatively charged CL in a membrane traps protons and increases their leakage, potentially in a manner dependent on membrane curvature. We discuss the possible mechanisms and implications of these findings for mitochondrial respiration function.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827254","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

Molecular insights into the elevator-type mechanism of the cyanobacterial bicarbonate transporter BicA. 对蓝藻碳酸氢盐转运体 BicA 电梯型机制的分子认识

IF 3.2 3区生物学

Biophysical journal Pub Date : 2024-12-13 DOI: 10.1016/j.bpj.2024.12.013

Matthew C Chan, Yazeed Alfawaz, Arnav Paul, Diwakar Shukla

{"title":"Molecular insights into the elevator-type mechanism of the cyanobacterial bicarbonate transporter BicA.","authors":"Matthew C Chan, Yazeed Alfawaz, Arnav Paul, Diwakar Shukla","doi":"10.1016/j.bpj.2024.12.013","DOIUrl":"10.1016/j.bpj.2024.12.013","url":null,"abstract":"Cyanobacteria are responsible for up to 80% of aquatic carbon dioxide fixation and have evolved a specialized carbon concentrating mechanism to increase photosynthetic yield. As such, cyanobacteria are attractive targets for synthetic biology and engineering approaches to address the demands of global energy security, food production, and climate change for an increasing world's population. The bicarbonate transporter BicA is a sodium-dependent, low-affinity, high-flux bicarbonate symporter expressed in the plasma membrane of cyanobacteria. Despite extensive biochemical characterization of BicA, including the resolution of the BicA crystal structure, the dynamic understanding of the bicarbonate transport mechanism remains elusive. To this end, we have collected over 1 ms of all-atom molecular dynamics simulation data of the BicA dimer to elucidate the structural rearrangements involved in the substrate transport process. We further characterized the energetics of the transition of BicA protomers and investigated potential mutations that are shown to decrease the free energy barrier of conformational transitions. In all, our study illuminates a detailed mechanistic understanding of the conformational dynamics of bicarbonate transporters and provides atomistic insights to engineering these transporters for enhanced photosynthetic production.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827252","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

Multiscale simulations reveal architecture of NOTCH protein and ligand specific features.

IF 3.2 3区生物学

Biophysical journal Pub Date : 2024-12-13 DOI: 10.1016/j.bpj.2024.12.014

Surabhi Rathore, Deepanshi Gahlot, Jesu Castin, Arastu Pandey, Shreyas Arvindekar, Shruthi Viswanath, Lipi Thukral

{"title":"Multiscale simulations reveal architecture of NOTCH protein and ligand specific features.","authors":"Surabhi Rathore, Deepanshi Gahlot, Jesu Castin, Arastu Pandey, Shreyas Arvindekar, Shruthi Viswanath, Lipi Thukral","doi":"10.1016/j.bpj.2024.12.014","DOIUrl":"10.1016/j.bpj.2024.12.014","url":null,"abstract":"NOTCH, a single-pass transmembrane protein, plays a crucial role in cell fate determination through cell-to-cell communication. It interacts with two canonical ligands, Delta-like (DLL) and Jagged (JAG), located on neighboring cells to regulate diverse cellular processes. Despite extensive studies on the functional roles of NOTCH and its ligands in cellular growth, the structural details of full-length NOTCH and its ligands remain poorly understood. In this study, we employed fragment-based modeling and multiscale simulations to study the full-length structure of the human NOTCH ectodomain, comprising 1756 amino acids. We performed coarse-grained dynamics simulations of NOTCH in both glycosylated and nonglycosylated forms to investigate the role of glycosylation in modulating its conformational dynamics. In apo form, coarse-grained simulations revealed that glycosylated NOTCH protein can transition from an elongated structure of ∼86 nm from the membrane surface to a semicompact state (∼23.81 ± 9.98 nm), which aligns with cryo-EM data. To transition from the apo form to ligand-bound forms of NOTCH, we followed an atomistic and integrative modeling approach to model the interactions between NOTCH-DLL4 and NOTCH-JAG1. Atomistic simulations of the smaller bound fragment EGF8-13 patch revealed conformational plasticity critical for NOTCH binding, while integrative modeling of full-length complexes suggested a larger binding surface than reported previously. Simulations of pathogenic mutations revealed that E360K and R448Q disrupted the NOTCH-ligand interaction surfaces, causing dissociation. In contrast, C1133Y in the Abruptex domain compromised protein stability by disrupting the domain's interaction with the ligand-binding domain in the apo form of NOTCH-ECD. These findings provide a detailed molecular understanding of NOTCH and its ligands, offering insights that could enable the development of novel therapeutic approaches to selectively target pathogenic NOTCH signaling.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827253","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

Lipid demixing reduces energy barriers for high-curvature vesicle budding. 脂质脱混可降低高曲率囊泡萌发的能量障碍

IF 3.2 3区生物学

Biophysical journal Pub Date : 2024-12-12 DOI: 10.1016/j.bpj.2024.12.012

Itay Schachter

引用次数: 0

Assembly landscape of the complete B-repeat superdomain from Staphylococcus epidermidis strain 1457.

IF 3.2 3区生物学

Biophysical journal Pub Date : 2024-12-11 DOI: 10.1016/j.bpj.2024.12.011

Alexander E Yarawsky, Andrew B Herr

{"title":"Assembly landscape of the complete B-repeat superdomain from Staphylococcus epidermidis strain 1457.","authors":"Alexander E Yarawsky, Andrew B Herr","doi":"10.1016/j.bpj.2024.12.011","DOIUrl":"10.1016/j.bpj.2024.12.011","url":null,"abstract":"The accumulation-associated protein (Aap) is the primary determinant of Staphylococcus epidermidis device-related infections. The B-repeat superdomain is responsible for intercellular adhesion that leads to the development of biofilms occurring in such infections. It was recently demonstrated that Zn-induced B-repeat assembly leads to formation of functional amyloid fibrils, which offer strength and stability to the biofilm. Rigorous biophysical studies of Aap B-repeats from S. epidermidis strain RP62A revealed Zn-induced assembly into stable, reversible dimers and tetramers, prior to aggregation into amyloid fibrils. Genetic manipulation is not tractable for many S. epidermidis strains, including RP62A; instead, many genetic studies have used strain 1457. Therefore, to better connect findings from biophysical and structural studies of B-repeats to in vivo studies, the B-repeat superdomain from strain 1457 was examined. Differences between the B-repeats from strains RP62A and 1457 include the number of B-repeats, which has been shown to play a critical role in assembly into amyloid fibrils, as well as the distribution of consensus and variant B-repeat subtypes, which differ in assembly competency and thermal stability. Detailed investigation of the Zn-induced assembly of the full B-repeat superdomain from strain 1457 was conducted using analytical ultracentrifugation. Whereas the previous construct from RP62A (Brpt5.5) formed a stable tetramer prior to aggregation, Brpt6.5 from 1457 forms extremely large stable species on the order of ≈28-mers, prior to aggregation into similar amyloid fibrils. Our data suggest that both assembly pathways may proceed through the same mechanism of dimerization and tetramerization, and both conclude with the formation of amyloid-like fibrils. Discussion of assembly behavior of B-repeats from different strains and of different length is provided with considerations of biological implications.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817034","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

Fine-tuning of Fgf8 morphogen gradient by heparan sulfate proteoglycans in the extracellular matrix.

IF 3.2 3区生物学

Biophysical journal Pub Date : 2024-12-11 DOI: 10.1016/j.bpj.2024.12.009

Mansi Gupta, Thomas Kurth, Fabian Heinemann, Petra Schwille, Sebastian Keil, Franziska Knopf, Michael Brand

{"title":"Fine-tuning of Fgf8 morphogen gradient by heparan sulfate proteoglycans in the extracellular matrix.","authors":"Mansi Gupta, Thomas Kurth, Fabian Heinemann, Petra Schwille, Sebastian Keil, Franziska Knopf, Michael Brand","doi":"10.1016/j.bpj.2024.12.009","DOIUrl":"10.1016/j.bpj.2024.12.009","url":null,"abstract":"Embryonic development is orchestrated by the action of morphogens, which spread out from a local source and activate, in a field of target cells, different cellular programs based on their concentration gradient. Fibroblast growth factor 8 (Fgf8) is a morphogen with important functions in embryonic organizing centers. It forms a gradient in the extracellular space by free diffusion, interaction with the extracellular matrix (ECM), and receptor-mediated endocytosis. However, morphogen gradient regulation by ECM is still poorly understood. Here, we show that specific heparan sulfate proteoglycans (HSPGs) bind Fgf8 with different affinities directly in the ECM of living zebrafish embryos, thus affecting its diffusion and signaling. Using single-molecule fluorescence correlation spectroscopy, we quantify this binding in vivo, and find two different modes of interaction. First, reducing or increasing the concentration of specific HSPGs in the extracellular space alters Fgf8 diffusion and, thus, its gradient shape. Second, ternary complex formation of Fgf8 ligand with Fgf receptors and HSPGs at the cell surface requires HSPG attachment to the cell membrane. Together, our results show that graded Fgf8 morphogen distribution is achieved by constraining free Fgf8 diffusion through successive interactions with HSPGs at the cell surface and in ECM space.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817036","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

Vibrational signatures of living cells.

IF 3.2 3区生物学

Biophysical journal Pub Date : 2024-12-10 DOI: 10.1016/j.bpj.2024.12.008

Oren Tchaicheeyan, Ramon Zaera Polo, Beth Mortimer, Ayelet Lesman

引用次数: 0

TGF-β2 enhances nanoscale cortex stiffness via condensation of cytoskeleton-focal adhesion plaque.

IF 3.2 3区生物学

Biophysical journal Pub Date : 2024-12-06 DOI: 10.1016/j.bpj.2024.12.007

Mengmeng Duan, Yi Liu, Caixia Pi, Yanfang Zhao, Yunfei Tian, Jing Xie

{"title":"TGF-β2 enhances nanoscale cortex stiffness via condensation of cytoskeleton-focal adhesion plaque.","authors":"Mengmeng Duan, Yi Liu, Caixia Pi, Yanfang Zhao, Yunfei Tian, Jing Xie","doi":"10.1016/j.bpj.2024.12.007","DOIUrl":"10.1016/j.bpj.2024.12.007","url":null,"abstract":"Physical spatiotemporal characteristics of cellular cortex dominate cell functions and even determine cell fate. The cellular cortex is able to reorganize to a dynamic steady status with changed stiffnesses once stimulated, and thus alter the physiological and pathological activities of almost all types of cells. TGF-β2, a potent pleiotropic growth factor, plays important roles in cartilage development, endochondral ossification, and cartilage diseases. However, it is not yet known whether TGF-β2 would alter the physical spatiotemporal characteristics of the cell cortex such as cortex stiffness, thereby affecting the function of chondrocytes. In this study, we investigated the influence of TGF-β2 on cellular cortex stiffness of chondrocytes and the underlying mechanism. We firstly detected TGF-β2-induced changes in cytoskeleton and focal adhesion plaque, which were closely related to cellular cortex stiffness. We then characterized the landscape of nanoscale cortex stiffness in individual chondrocytes induced by TGF-β2 via atomic force microscopy. By using inhibitors, latrunculin A and blebbistatin, we verified the importance of cytoskeleton-focal adhesion plaque axis on cellular cortex stiffness of chondrocytes induced by TGF-β2. We finally elucidated that TGF-β2 enhanced the phosphorylation of Smad3 and facilitated the nuclear accumulation of p-Smad3. The p-Smad3 aggregated in the nuclei enhanced the cytoskeleton and focal adhesion plaque at transcriptional level, thereby mediating changes in cell cortex stiffness. Taken together, these results provide an understanding about the role of TGF-β2 on physical spatiotemporal properties of cell cortex in chondrocytes, and might provide cues for interpretation of cartilage development and interventions to cartilage diseases.","PeriodicalId":8922,"journal":{"name":"Biophysical journal","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791157","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

Energy-based bond graph models of glucose transport with SLC transporters.

IF 3.2 3区生物学

Biophysical journal Pub Date : 2024-12-06 DOI: 10.1016/j.bpj.2024.12.006

Peter J Hunter, Weiwei Ai, David P Nickerson

引用次数: 0