arXiv - QuanBio - Subcellular Processes最新文献

Causal loop and Stock-Flow Modeling of Signal Transduction Pathways 信号转导途径的因果循环和库存流模型

arXiv - QuanBio - Subcellular Processes Pub Date : 2024-09-02 DOI: arxiv-2409.01267

Sadegh Sulaimany, Gholamreza Bidkhori, Sarbaz H. A. Khoshnaw

{"title":"Causal loop and Stock-Flow Modeling of Signal Transduction Pathways","authors":"Sadegh Sulaimany, Gholamreza Bidkhori, Sarbaz H. A. Khoshnaw","doi":"arxiv-2409.01267","DOIUrl":"https://doi.org/arxiv-2409.01267","url":null,"abstract":"System dynamics is a popular approach in many fields of science and\u0000technology, but it has not been investigated for cell signaling pathways yet.\u0000It is a well formulated methodology used to analyze the components of a system\u0000considering the cause-effect relationships. The two main components of system\u0000dynamics modeling, Causal Loop and Stocks-Flow diagrams, make possible to model\u0000the dynamics of the system with the ability to analyze it both qualitatively\u0000and quantitatively. In this paper, after introducing the system dynamics\u0000modeling approach, and giving a simple example from its usage for Michaelis\u0000Menton reactions, a three-step process is proposed for signal transduction\u0000modeling. Then in a complete example, it is applied to a case study in cell\u0000signaling pathways, namely the RKIP Influence on the ERK signaling pathway and\u0000the results is compared with an integrative modeling approach based on Petri\u0000net and ODEs. Computational simulations show the success of the system dynamic\u0000in easier and effective modeling of the cell signaling pathways, in addition to\u0000its diverse options for understanding and testing the pathway quantitatively\u0000and quantitatively at the same time in relation to other methods. More\u0000intestinally, the suggested approach here helps one to identify all biochemical\u0000reaction paths and loops for complex cell signaling pathways. It will be a good\u0000step forward to define dominant systems for such complex cell signaling\u0000pathways.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142192217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transient contacts between filaments impart its elasticity to branched actin 丝之间的瞬时接触赋予支链肌动蛋白弹性

arXiv - QuanBio - Subcellular Processes Pub Date : 2024-08-31 DOI: arxiv-2409.00549

Mehdi Bouzid, Cesar Valencia Gallardo, Magdalena Kopec, Lara Koehler, Giuseppe Foffi, Olivia du Roure, Julien Heuvingh, Martin Lenz

引用次数: 0

Ultra-rapid, Quantitative, Label-free Antibiotic Susceptibility Testing via Optically Detected Purine Metabolites 通过光学检测嘌呤代谢物进行超快速、定量、无标记抗生素敏感性测试

arXiv - QuanBio - Subcellular Processes Pub Date : 2024-08-30 DOI: arxiv-2408.16996

Ranjith Premasiri, Allen Fraiman, Lawrence Ziegler

{"title":"Ultra-rapid, Quantitative, Label-free Antibiotic Susceptibility Testing via Optically Detected Purine Metabolites","authors":"Ranjith Premasiri, Allen Fraiman, Lawrence Ziegler","doi":"arxiv-2408.16996","DOIUrl":"https://doi.org/arxiv-2408.16996","url":null,"abstract":"There is an urgent need for the development of novel and truly rapid (equal\u0000or less than 1 hour) antibiotic susceptibility testing (AST) platforms in order\u0000to provide best antimicrobial prescribing practices and to help reduce the\u0000increasing global threat of antibiotic resistance. A 785 nm surface enhanced\u0000Raman spectroscopy (SERS) based phenotypic methodology is described that\u0000results in accurate minimum inhibitory concentration (MIC) determinations for\u0000all tested strain-antibiotic pairs. The SERS-AST procedure results in accurate\u0000MICs, the key quantitative measure of in vitro drug susceptibility, in 1 hour,\u0000including a 30-minute incubation period. The method is effective for both Gram\u0000positive and negative species, and for antibiotics with different initial\u0000primary targets of antibiotic activity, and for both bactericidal and\u0000bacteriostatic antibiotics. The molecular level mechanism of this methodology\u0000is described. Bacterial SERS spectra are due to secreted purine nucleotide\u0000degradation products (principally adenine, guanine, xanthine and hypoxanthine)\u0000resulting from water washing induced bacterial stringent response and the\u0000resulting (p)ppGpp alarmone mediates nucleobase formation from unneeded tRNA\u0000and rRNA. The rewiring of metabolic responses resulting from the secondary\u0000metabolic effects of antibiotic exposure during the 30-minute incubation period\u0000accounts for the dose dependence of the SERS spectral intensities which are\u0000used to accurately yield the MIC. This is the fastest demonstrated AST method\u0000yielding MICs.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142192219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intracellular order formation through stepwise phase transitions 通过逐步相变形成细胞内秩序

arXiv - QuanBio - Subcellular Processes Pub Date : 2024-08-26 DOI: arxiv-2408.14242

Yuika Ueda, Shinji Deguchi

{"title":"Intracellular order formation through stepwise phase transitions","authors":"Yuika Ueda, Shinji Deguchi","doi":"arxiv-2408.14242","DOIUrl":"https://doi.org/arxiv-2408.14242","url":null,"abstract":"Living cells inherently exhibit the ability to spontaneously reorganize their\u0000structures in response to changes in both their internal and external\u0000environments. Among these responses, the organization of stress fibers composed\u0000of actin molecules changes in direct accordance with the mechanical stiffness\u0000of their environments. On soft substrates, SFs are rarely formed, but as\u0000stiffness increases, they emerge with random orientation, progressively align,\u0000and eventually form thicker bundles as stiffness surpasses successive\u0000thresholds. These transformations share similarities with phase transitions\u0000studied in condensed matter physics, yet despite extensive research on cellular\u0000dynamics, the introduction of the statistical mechanics perspective to the\u0000environmental dependence of intracellular structures remains underexplored.\u0000With this physical framework, we identify key relationships governing these\u0000intracellular transitions, highlighting the delicate balance between energy and\u0000entropy. Our analysis provides a unified understanding of the stepwise phase\u0000transitions of actin structures, offering new insights into related biological\u0000mechanisms. Notably, our study suggests the existence of mechanical checkpoints\u0000in the G1 phase of the cell cycle, which sequentially regulate the formation of\u0000intracellular structures to ensure proper cell cycle progression.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142192220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Novel Use of Pseudospectra in Mathematical Biology: Understanding HPA Axis Sensitivity 伪谱在数学生物学中的新用途：了解 HPA 轴的敏感性

arXiv - QuanBio - Subcellular Processes Pub Date : 2024-08-01 DOI: arxiv-2408.00845

Catherine Drysdale, Matthew J. Colbrook

{"title":"A Novel Use of Pseudospectra in Mathematical Biology: Understanding HPA Axis Sensitivity","authors":"Catherine Drysdale, Matthew J. Colbrook","doi":"arxiv-2408.00845","DOIUrl":"https://doi.org/arxiv-2408.00845","url":null,"abstract":"The Hypothalamic-Pituitary-Adrenal (HPA) axis is a major neuroendocrine\u0000system, and its dysregulation is implicated in various diseases. This system\u0000also presents interesting mathematical challenges for modeling. We consider a\u0000nonlinear delay differential equation model and calculate pseudospectra of\u0000three different linearizations: a time-dependent Jacobian, linearization around\u0000the limit cycle, and dynamic mode decomposition (DMD) analysis of Koopman\u0000operators (global linearization). The time-dependent Jacobian provided insight\u0000into experimental phenomena, explaining why rats respond differently to\u0000perturbations during corticosterone secretion's upward versus downward slopes.\u0000We developed new mathematical techniques for the other two linearizations to\u0000calculate pseudospectra on Banach spaces and apply DMD to delay differential\u0000equations, respectively. These methods helped establish local and global limit\u0000cycle stability and study transients. Additionally, we discuss using\u0000pseudospectra to substantiate the model in experimental contexts and establish\u0000bio-variability via data-driven methods. This work is the first to utilize\u0000pseudospectra to explore the HPA axis.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141942899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Heterogeneous model for superdiffusive movement of dense-core vesicles in C. elegans 致密核心囊泡在 elegans 中超扩散运动的异质模型

arXiv - QuanBio - Subcellular Processes Pub Date : 2024-07-25 DOI: arxiv-2407.18237

Anna Gavrilova, Nickolay Korabel, Victoria J. Allan, Sergei Fedotov

{"title":"Heterogeneous model for superdiffusive movement of dense-core vesicles in C. elegans","authors":"Anna Gavrilova, Nickolay Korabel, Victoria J. Allan, Sergei Fedotov","doi":"arxiv-2407.18237","DOIUrl":"https://doi.org/arxiv-2407.18237","url":null,"abstract":"Transport of dense core vesicles (DCVs) in neurons is crucial for\u0000distributing molecules like neuropeptides and growth factors. We studied the\u0000experimental trajectories of dynein-driven directed movement of DCVs in the ALA\u0000neuron C. elegans over a duration of up to 6 seconds. We analysed the DCV\u0000movement in three strains of C. elegans: 1) with normal kinesin-1 function, 2)\u0000with reduced function in kinesin light chain 2 (KLC-2), and 3) a null mutation\u0000in kinesin light chain 1 (KLC-1). We find that DCVs move superdiffusively with\u0000displacement variance $var(x) sim t^2$ in all three strains with low reversal\u0000rates and frequent immobilization of DCVs. The distribution of DCV\u0000displacements fits a beta-binomial distribution with the mean and the variance\u0000following linear and quadratic growth patterns, respectively. We propose a\u0000simple heterogeneous random walk model to explain the observed superdiffusive\u0000retrograde transport behaviour of DCV movement. This model involves a random\u0000probability with the beta density for a DCV to resume its movement or remain in\u0000the same position.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141777653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Voltage mapping in subcellular nanodomains using electro-diffusion modeling 利用电扩散建模绘制亚细胞纳米域的电压分布图

arXiv - QuanBio - Subcellular Processes Pub Date : 2024-07-22 DOI: arxiv-2407.15697

Frédéric Paquin-Lefebvre, David Holcman

{"title":"Voltage mapping in subcellular nanodomains using electro-diffusion modeling","authors":"Frédéric Paquin-Lefebvre, David Holcman","doi":"arxiv-2407.15697","DOIUrl":"https://doi.org/arxiv-2407.15697","url":null,"abstract":"Voltage distribution in sub-cellular micro-domains such as neuronal synapses,\u0000small protrusions or dendritic spines regulates the opening and closing of\u0000ionic channels, energy production and thus cellular homeostasis and\u0000excitability. Yet how voltage changes at such a small scale in vivo remains\u0000challenging due to the experimental diffraction limit, large signal\u0000fluctuations and the still limited resolution of fast voltage indicators. Here,\u0000we study the voltage distribution in nano-compartments using a computational\u0000approach based on the Poisson-Nernst-Planck equations for the electro-diffusion\u0000motion of ions, where inward and outward fluxes are generated between channels.\u0000We report a current-voltage (I-V) logarithmic relationship generalizing Nernst\u0000law that reveals how the local membrane curvature modulates the voltage. We\u0000further find that an influx current penetrating a cellular electrolyte can lead\u0000to perturbations from tens to hundreds of nanometers deep depending on the\u0000local channels organization. Finally, we show that the neck resistance of\u0000dendritic spines can be completely shunted by the transporters located on the\u0000head boundary, facilitating ionic flow. To conclude, we propose that voltage is\u0000regulated at a subcellular level by channels organization, membrane curvature\u0000and narrow passages.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141777773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Spatiotemporal dynamics of ionic reorganization near biological membrane interfaces 生物膜界面附近离子重组的时空动力学

arXiv - QuanBio - Subcellular Processes Pub Date : 2024-07-16 DOI: arxiv-2407.11947

Hyeongjoo Row, Joshua B. Fernandes, Kranthi K. Mandadapu, Karthik Shekhar

{"title":"Spatiotemporal dynamics of ionic reorganization near biological membrane interfaces","authors":"Hyeongjoo Row, Joshua B. Fernandes, Kranthi K. Mandadapu, Karthik Shekhar","doi":"arxiv-2407.11947","DOIUrl":"https://doi.org/arxiv-2407.11947","url":null,"abstract":"Electrical signals in excitable cells involve spatially localized ionic\u0000fluxes through ion channels and pumps on cellular lipid membranes. Common\u0000approaches to understand how these localized fluxes spread assume that the\u0000membrane and the surrounding electrolyte comprise an equivalent circuit of\u0000capacitors and resistors, which ignores the localized nature of transmembrane\u0000ion transport, the resulting ionic gradients and electric fields, and their\u0000spatiotemporal relaxation. Here, we consider a model of localized ion pumping\u0000across a lipid membrane, and use theory and simulation to investigate how the\u0000electrochemical signal propagates spatiotemporally in- and out-of-plane along\u0000the membrane. The localized pumping generates long-ranged electric fields with\u0000three distinct scaling regimes along the membrane: a constant potential\u0000near-field region, an intermediate \"monopolar\" region, and a far-field\u0000\"dipolar\" region. Upon sustained pumping, the monopolar region expands radially\u0000in-plane with a steady speed that is enhanced by the dielectric mismatch and\u0000the finite thickness of the lipid membrane. For unmyelinated lipid membranes in\u0000physiological settings, we find remarkably fast propagation speeds of $sim!40\u0000, mathrm{m/s}$, allowing faster ionic reorganization compared to bare\u0000diffusion. Together, our work shows that transmembrane ionic fluxes induce\u0000transient long-ranged electric fields in electrolyte solutions, which may play\u0000hitherto unappreciated roles in biological signaling.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"65 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141720258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Diffusion-driven self-assembly of emerin nanodomains at the nuclear envelope 扩散驱动的核膜萌素纳米域自组装

arXiv - QuanBio - Subcellular Processes Pub Date : 2024-07-16 DOI: arxiv-2407.11758

Carlos D. Alas, Liying Wu, Fabien Pinaud, Christoph A. Haselwandter

引用次数: 0

The positioning of stress fibers in contractile cells minimizes internal mechanical stress 收缩细胞中应力纤维的定位可最大限度地减少内部机械应力

arXiv - QuanBio - Subcellular Processes Pub Date : 2024-07-10 DOI: arxiv-2407.07797

Lukas RiedelHeidelberg University, Valentin WössnerHeidelberg University, Dominic KempfHeidelberg University, Falko ZiebertHeidelberg University, Peter BastianHeidelberg University, Ulrich S. SchwarzHeidelberg University

{"title":"The positioning of stress fibers in contractile cells minimizes internal mechanical stress","authors":"Lukas RiedelHeidelberg University, Valentin WössnerHeidelberg University, Dominic KempfHeidelberg University, Falko ZiebertHeidelberg University, Peter BastianHeidelberg University, Ulrich S. SchwarzHeidelberg University","doi":"arxiv-2407.07797","DOIUrl":"https://doi.org/arxiv-2407.07797","url":null,"abstract":"The mechanics of animal cells is strongly determined by stress fibers, which\u0000are contractile filament bundles that form dynamically in response to\u0000extracellular cues. Stress fibers allow the cell to adapt its mechanics to\u0000environmental conditions and to protect it from structural damage. While the\u0000physical description of single stress fibers is well-developed, much less is\u0000known about their spatial distribution on the level of whole cells. Here, we\u0000combine a finite element method for one-dimensional fibers embedded in an\u0000elastic bulk medium with dynamical rules for stress fiber formation based on\u0000genetic algorithms. We postulate that their main goal is to achieve minimal\u0000mechanical stress in the bulk material with as few fibers as possible. The\u0000fiber positions and configurations resulting from this optimization task alone\u0000are in good agreement with those found in experiments where cells in\u00003D-scaffolds were mechanically strained at one attachment point. For optimized\u0000configurations, we find that stress fibers typically run through the cell in a\u0000diagonal fashion, similar to reinforcement strategies used for composite\u0000material.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141588242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0