arXiv - QuanBio - Subcellular Processes最新文献

{"title":"Principles of bursty mRNA expression and irreversibility in single cells and extrinsically varying populations","authors":"James Holehouse","doi":"arxiv-2405.12897","DOIUrl":"https://doi.org/arxiv-2405.12897","url":null,"abstract":"The canonical model of mRNA expression is the telegraph model, describing a\u0000gene that switches on and off, subject to transcription and decay. It describes\u0000steady-state mRNA distributions that subscribe to transcription in bursts with\u0000first-order decay, referred to as super-Poissonian expression. Using a\u0000telegraph-like model, I propose an answer to the question of why gene\u0000expression is bursty in the first place, and what benefits it confers. Using\u0000analytics for the entropy production rate, I find that entropy production is\u0000maximal when the on and off switching rates between the gene states are\u0000approximately equal. This is related to a lower bound on the free energy\u0000necessary to keep the system out of equilibrium, meaning that bursty gene\u0000expression may have evolved in part due to free energy efficiency. It is shown\u0000that there are trade-offs between having slow nuclear export, which can reduce\u0000cytoplasmic mRNA noise, and the energy required to keep the system out of\u0000equilibrium -- nuclear compartmentalization comes with an associated free\u0000energy cost. At the population level, I find that extrinsic variation,\u0000manifested in cell-to-cell differences in kinetic parameters, can make the\u0000system more or less reversible -- and potentially energy efficient -- depending\u0000on where the noise is located. This highlights that there evolutionary\u0000constraints on the suppression of extrinsic noise, whose origin is in cellular\u0000heterogeneity, in addition to intrinsic randomness arising from molecular\u0000collisions. Finally, I investigate the partially observed nature of most mRNA\u0000expression data which seems to obey detailed balance, yet remains unavoidably\u0000out-of-equilibrium.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141149197","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}

{"title":"Coat stiffening explains the consensus pathway of clathrin-mediated endocytosis","authors":"Felix FreyIST Austria, Ulrich S. SchwarzHeidelberg University","doi":"arxiv-2405.02820","DOIUrl":"https://doi.org/arxiv-2405.02820","url":null,"abstract":"Clathrin-mediated endocytosis is the main pathway used by eukaryotic cells to\u0000take up extracellular material, but the dominant physical mechanisms driving\u0000this process are still elusive. Recently several high-resolution imaging\u0000techniques have been used on different cell lines to measure the geometrical\u0000properties of clathrin-coated pits over their whole lifetime. Here we first\u0000show that all datasets follow the same consensus pathway, which is well\u0000described by the recently introduced cooperative curvature model, which\u0000predicts a flat-to curved transition at finite area, followed by linear growth\u0000and subsequent saturation of curvature. We then apply an energetic model for\u0000the composite of plasma membrane and clathrin coat to the consensus pathway to\u0000show that the dominant mechanism for invagination is coat stiffening, which\u0000results from cooperative interactions between the different clathrin molecules\u0000and progressively drives the system towards its intrinsic curvature. Our theory\u0000predicts that two length scales determine the time course of invagination,\u0000namely the patch size at which the flat-to-curved transition occurs and the\u0000final pit radius.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"152 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140885078","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}

{"title":"A Decade in a Systematic Review: The Evolution and Impact of Cell Painting","authors":"Srijit Seal, Maria-Anna Trapotsi, Ola Spjuth, Shantanu Singh, Jordi Carreras-Puigvert, Nigel Greene, Andreas Bender, Anne E. Carpenter","doi":"arxiv-2405.02767","DOIUrl":"https://doi.org/arxiv-2405.02767","url":null,"abstract":"High-content image-based assays have fueled significant discoveries in the\u0000life sciences in the past decade (2013-2023), including novel insights into\u0000disease etiology, mechanism of action, new therapeutics, and toxicology\u0000predictions. Here, we systematically review the substantial methodological\u0000advancements and applications of Cell Painting. Advancements include\u0000improvements in the Cell Painting protocol, assay adaptations for different\u0000types of perturbations and applications, and improved methodologies for feature\u0000extraction, quality control, and batch effect correction. Moreover, machine\u0000learning methods recently surpassed classical approaches in their ability to\u0000extract biologically useful information from Cell Painting images. Cell\u0000Painting data have been used alone or in combination with other -omics data to\u0000decipher the mechanism of action of a compound, its toxicity profile, and many\u0000other biological effects. Overall, key methodological advances have expanded\u0000the ability of Cell Painting to capture cellular responses to various\u0000perturbations. Future advances will likely lie in advancing computational and\u0000experimental techniques, developing new publicly available datasets, and\u0000integrating them with other high-content data types.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140885077","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}

{"title":"A Simple Comparison of Biochemical Systems Theory and Metabolic Control Analysis","authors":"Herbert MM Sauro","doi":"arxiv-2405.00810","DOIUrl":"https://doi.org/arxiv-2405.00810","url":null,"abstract":"This paper explores some basic concepts of Biochemical Systems Theory (BST)\u0000and Metabolic Control Analysis (MCA), two frameworks developed to understand\u0000the behavior of biochemical networks. Initially introduced by Savageau, BST\u0000focuses on system stability and employs power laws in modeling biochemical\u0000systems. On the other hand, MCA, pioneered by authors such as Kacser and Burns\u0000and Heinrich and Rapoport, emphasizes linearization of the governing equations\u0000and describes relationships (known as theorems) between different measures.\u0000Despite apparent differences, both frameworks are shown to be equivalent in\u0000many respects. Through a simple example of a linear chain, the paper\u0000demonstrates how BST and MCA yield identical results when analyzing\u0000steady-state behavior and logarithmic gains within biochemical pathways. This\u0000comparative analysis highlights the interchangeability of concepts such as\u0000kinetic orders, elasticities and other logarithmic gains.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"60 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140837593","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}

{"title":"Polymer Collapse and Liquid-Liquid Phase-Separation are Coupled in a Generalized Prewetting Transition","authors":"Mason N. Rouches, Benjamin B. Machta","doi":"arxiv-2404.19158","DOIUrl":"https://doi.org/arxiv-2404.19158","url":null,"abstract":"The three-dimensional organization of chromatin is thought to play an\u0000important role in controlling gene expression. Specificity in expression is\u0000achieved through the interaction of transcription factors and other nuclear\u0000proteins with particular sequences of DNA. At unphysiological concentrations\u0000many of these nuclear proteins can phase-separate in the absence of DNA, and it\u0000has been hypothesized that, in vivo, the thermodynamic forces driving these\u0000phases help determine chromosomal organization. However it is unclear how DNA,\u0000itself a long polymer subject to configurational transitions, interacts with\u0000three-dimensional protein phases. Here we show that a long compressible polymer\u0000can be coupled to interacting protein mixtures, leading to a generalized\u0000prewetting transition where polymer collapse is coincident with a locally\u0000stabilized liquid droplet. We use lattice Monte-Carlo simulations and a\u0000mean-field theory to show that these phases can be stable even in regimes where\u0000both polymer collapse and coexisting liquid phases are unstable in isolation,\u0000and that these new transitions can be either abrupt or continuous. For polymers\u0000with internal linear structure we further show that changes in the\u0000concentration of bulk components can lead to changes in three-dimensional\u0000polymer structure. In the nucleus there are many distinct proteins that\u0000interact with many different regions of chromatin, potentially giving rise to\u0000many different Prewet phases. The simple systems we consider here highlight\u0000chromatin's role as a lower-dimensional surface whose interactions with\u0000proteins are required for these novel phases.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140837662","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}

{"title":"Bacterial stress granule protects mRNA through ribonucleases exclusion","authors":"Linsen Pei, Yujia Xian, Xiaodan Yan, Charley Schaefer, Aisha H. Syeda, Jamieson Howard, Hebin Liao, Fan Bai, Mark C. Leake, Yingying Pu","doi":"arxiv-2404.17873","DOIUrl":"https://doi.org/arxiv-2404.17873","url":null,"abstract":"Membraneless droplets formed through liquid-liquid phase separation (LLPS)\u0000play a crucial role in mRNA storage, enabling organisms to swiftly respond to\u0000environmental changes. However, the mechanisms underlying mRNA integration and\u0000protection within droplets remain unclear. Here, we unravel the role of\u0000bacterial aggresomes as stress granules (SGs) in safeguarding mRNA during\u0000stress. We discovered that upon stress onset, mobile mRNA molecules selectively\u0000incorporate into individual proteinaceous SGs based on length-dependent\u0000enthalpic gain over entropic loss. As stress prolongs, SGs undergo compaction\u0000facilitated by stronger non-specific RNA-protein interactions, thereby\u0000promoting recruitment of shorter RNA chains. Remarkably, mRNA ribonucleases are\u0000repelled from bacterial SGs, due to the influence of protein surface charge.\u0000This exclusion mechanism ensures the integrity and preservation of mRNA within\u0000SGs during stress conditions, explaining how mRNA can be stored and protected\u0000from degradation. Following stress removal, SGs facilitate mRNA translation,\u0000thereby enhancing cell fitness in changing environments. These droplets\u0000maintain mRNA physiological activity during storage, making them an intriguing\u0000new candidate for mRNA therapeutics manufacturing.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"60 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140837810","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}

{"title":"Spatio-Temporal Dynamics of Nucleo-Cytoplasmic Transport","authors":"S. Alex Rautu, Alexandra Zidovska, Michael J. Shelley","doi":"arxiv-2404.06688","DOIUrl":"https://doi.org/arxiv-2404.06688","url":null,"abstract":"Nucleocytoplasmic transport is essential for cellular function, presenting a\u0000canonical example of rapid molecular sorting inside cells. It consists of a\u0000coordinated interplay between import/export of molecules in/out the cell\u0000nucleus. Here, we investigate the role of spatio-temporal dynamics of the\u0000nucleocytoplasmic transport and its regulation. We develop a biophysical model\u0000that captures the main features of the nucleocytoplasmic transport, in\u0000particular, its regulation through the Ran cycle. Our model yields steady-state\u0000profiles for the molecular components of the Ran cycle, their relaxation times,\u0000as well as the nuclear-to-cytoplasmic molecule ratio. We show that these\u0000quantities are affected by their spatial dynamics and heterogeneity within the\u0000nucleus. Specifically, we find that the spatial nonuniformity of Ran Guanine\u0000Exchange Factor (RanGEF) -- particularly its proximity to the nuclear envelope\u0000-- enhances the Ran cycle's efficiency. We further show that RanGEF's\u0000accumulation near the nuclear envelope results from its intrinsic dynamics as a\u0000nuclear cargo, transported by the Ran cycle itself. Overall, our work\u0000highlights the critical role of molecular spatial dynamics in cellular\u0000processes, and proposes new avenues for theoretical and experimental inquiries\u0000into the nucleocytoplasmic transport.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140578699","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}

{"title":"Force generation by a cylindrical cell under stationary osmolytes synthesis","authors":"Wei-Yuan Kong, Antonio Mosciatti Jofré, Manon Quiros, Marie-Béatrice Bogeat-Triboulot, Evelyne Kolb, Etienne Couturier","doi":"arxiv-2403.18401","DOIUrl":"https://doi.org/arxiv-2403.18401","url":null,"abstract":"Turgor is the driving force of plant growth, making possible for roots to\u0000overcome soil resistance or for stems to counteract gravity. Maintaining a\u0000constant growth rate while avoiding the cell content dilution, which would\u0000progressively stop the inward water flux, imposes the production or import of\u0000osmolytes in proportion to the increase of volume. We coin this phenomenon\u0000stationary osmoregulation. The article explores the quantitative consequences\u0000of this hypothesis on the interaction of a cylindrical cell growing axially\u0000against an obstacle. An instantaneous axial compression of a pressurized cylindrical cell\u0000generates a force and a pressure jump which both decrease toward a lower value\u0000once water has flowed out of the cell to reach the water potential equilibrium.\u0000In a first part, the article derives analytical formula for these force and\u0000over-pressure both before and after relaxation. In a second part, we describe\u0000how the coupling of the Lockhart's growth law with the stationary\u0000osmoregulation hypothesis predicts a transient slowdown in growth due to\u0000contact before a re-acceleration in growth. We finally compare these\u0000predictions with the output of an elastic growth model which ignores the\u0000osmotic origin of growth: models only match in the early phase of contact for\u0000high stiffness obstacle.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"87 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140312883","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}

{"title":"Comprehensive Lipidomic Automation Workflow using Large Language Models","authors":"Connor Beveridge, Sanjay Iyer, Caitlin E. Randolph, Matthew Muhoberac, Palak Manchanda, Amy C. Clingenpeel, Shane Tichy, Gaurav Chopra","doi":"arxiv-2403.15076","DOIUrl":"https://doi.org/arxiv-2403.15076","url":null,"abstract":"Lipidomics generates large data that makes manual annotation and\u0000interpretation challenging. Lipid chemical and structural diversity with\u0000structural isomers further complicates annotation. Although, several commercial\u0000and open-source software for targeted lipid identification exists, it lacks\u0000automated method generation workflows and integration with statistical and\u0000bioinformatics tools. We have developed the Comprehensive Lipidomic Automated\u0000Workflow (CLAW) platform with integrated workflow for parsing, detailed\u0000statistical analysis and lipid annotations based on custom multiple reaction\u0000monitoring (MRM) precursor and product ion pair transitions. CLAW contains\u0000several modules including identification of carbon-carbon double bond\u0000position(s) in unsaturated lipids when combined with ozone electrospray\u0000ionization (OzESI)-MRM methodology. To demonstrate the utility of the automated\u0000workflow in CLAW, large-scale lipidomics data was collected with traditional\u0000and OzESI-MRM profiling on biological and non-biological samples. Specifically,\u0000a total of 1497 transitions organized into 10 MRM-based mass spectrometry\u0000methods were used to profile lipid droplets isolated from different brain\u0000regions of 18-24 month-old Alzheimer's disease mice and age-matched wild-type\u0000controls. Additionally, triacyclglycerols (TGs) profiles with carbon-carbon\u0000double bond specificity were generated from canola oil samples using OzESI-MRM\u0000profiling. We also developed an integrated language user interface with large\u0000language models using artificially intelligent (AI) agents that permits users\u0000to interact with the CLAW platform using a chatbot terminal to perform\u0000statistical and bioinformatic analyses. We envision CLAW pipeline to be used in\u0000high-throughput lipid structural identification tasks aiding users to generate\u0000automated lipidomics workflows ranging from data acquisition to AI agent-based\u0000bioinformatic analysis.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140297614","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}

{"title":"Enlightening the blind spot of the Michaelis-Menten rate law: The role of relaxation dynamics in molecular complex formation","authors":"Junghun Chae, Roktaek Lim, Thomas L. P. Martin, Cheol-Min Ghim, Pan-Jun Kim","doi":"arxiv-2403.11979","DOIUrl":"https://doi.org/arxiv-2403.11979","url":null,"abstract":"The century-long Michaelis-Menten rate law and its modifications in the\u0000modeling of biochemical rate processes stand on the assumption that the\u0000concentration of the complex of interacting molecules, at each moment, rapidly\u0000approaches an equilibrium (quasi-steady state) compared to the pace of\u0000molecular concentration changes. Yet, in the case of actively time-varying\u0000molecular concentrations with transient or oscillatory dynamics, the deviation\u0000of the complex profile from the quasi-steady state becomes relevant. A recent\u0000theoretical approach, known as the effective time-delay scheme (ETS), suggests\u0000that the delay by the relaxation time of molecular complex formation\u0000contributes to the substantial breakdown of the quasi-steady state assumption.\u0000Here, we systematically expand this ETS and inquire into the comprehensive\u0000roles of relaxation dynamics in complex formation. Through the modeling of\u0000rhythmic protein-protein and protein-DNA interactions and the mammalian\u0000circadian clock, our analysis reveals the effect of the relaxation dynamics\u0000beyond the time delay, which extends to the dampening of changes in the complex\u0000concentration with a reduction in the oscillation amplitude against the\u0000quasi-steady state. Interestingly, the combined effect of the time delay and\u0000amplitude reduction shapes both qualitative and quantitative oscillatory\u0000patterns such as the emergence and variability of the mammalian circadian\u0000rhythms. These findings highlight the drawback of the routine assumption of\u0000quasi-steady states and enhance the mechanistic understanding of rich\u0000time-varying biomolecular activities.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"119 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140170996","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}