Goutham Kodakandla, Askar Akimzhanov, Darren Boehning
{"title":"Regulation of store-operated calcium entry","authors":"Goutham Kodakandla, Askar Akimzhanov, Darren Boehning","doi":"arxiv-2309.06907","DOIUrl":"https://doi.org/arxiv-2309.06907","url":null,"abstract":"Plasma membrane calcium influx through ion channels is crucial for many\u0000events in cellular physiology. Cell surface stimuli lead to the production of\u0000inositol 1,4,5-trisphosphate (IP3), which binds to IP3 receptors in the\u0000endoplasmic reticulum (ER) to release calcium pools from the ER lumen. This\u0000leads to depletion of ER calcium pools which has been termed store-depletion.\u0000Store-depletion leads the dissociation of calcium ions from the EF-hand motif\u0000of the ER calcium sensor Stromal Interaction Molecule 1 (STIM1). This leads to\u0000a conformational change in STIM1 which helps it to interact with a plasma\u0000membrane (PM) at ER:PM junctions. At these ER:PM junctions, STIM1 binds to and\u0000activates a calcium channel known as Orai1 to form calcium-release activated\u0000calcium (CRAC) channels. Activation of Orai1 leads to calcium influx, known as\u0000store-operated calcium entry (SOCE). In addition to Orai1 and STIM1, the\u0000homologs of Orai1 and STIM1, such as Orai2/3 and STIM2 also play a crucial role\u0000in calcium homeostasis. The influx of calcium through the Orai channel\u0000activates a calcium current that has been termed CRAC currents. CRAC channels\u0000form multimers and cluster together in large macromolecular assemblies termed\u0000puncta. How these CRAC channels form puncta has been contentious since their\u0000discovery. In this review, we will outline the history of SOCE, the molecular\u0000players involved in this process (Orai and STIM proteins, TRP channels,\u0000SOCE-associated regulatory factor etc.), as well as the models that have been\u0000proposed to explain this important mechanism in cellular physiology.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"51 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138511128","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":"Newcomb-Benford Law in Neuromuscular Transmission: Validation at Hyperkalemic Conditions","authors":"Adriano Silva, Sergio Floquet, Ricardo Lima","doi":"arxiv-2309.06965","DOIUrl":"https://doi.org/arxiv-2309.06965","url":null,"abstract":"Recently, we demonstrated the validity of anomalous numbers law, known as\u0000Newcomb-Benford's law, at the mammalian neuromuscular transmission, considering\u0000different extracellular calcium concentrations arXiv:2002.01986. The present\u0000work continues to examine how alterations in extracellular solution modulate\u0000the first digit law in the context of the spontaneous release of acetylcholine\u0000from the neuromuscular junction. We investigated if the intervals of miniature\u0000potentials collected at the neuromuscular junction obey the law in a\u0000hyperkalemic environment. The analysis showed that the interval between the\u0000miniature potentials at high potassium concentrations follows Newcomb-Benford's\u0000law. Also, our data allowed us to uncover a conformity fluctuation as a\u0000function of the number of intervals of the miniature potentials. Finally, we\u0000discuss the biophysical implications of the present findings.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"51 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138511129","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}
Shankar Sivarajan, Yu Shi, Katherine M. Xiang, Clary Rodríguez-Cruz, Christopher L. Porter, Geran M. Kostecki, Leslie Tung, John C. Crocker, Daniel H. Reich
{"title":"Lévy distributed fluctuations in the living cell cortex","authors":"Shankar Sivarajan, Yu Shi, Katherine M. Xiang, Clary Rodríguez-Cruz, Christopher L. Porter, Geran M. Kostecki, Leslie Tung, John C. Crocker, Daniel H. Reich","doi":"arxiv-2309.06226","DOIUrl":"https://doi.org/arxiv-2309.06226","url":null,"abstract":"The actomyosin cortex is an active material that provides animal cells with a\u0000strong but flexible exterior, whose mechanics, including non-Gaussian\u0000fluctuations and occasional large displacements or cytoquakes, have defied\u0000explanation. We study the active nanoscale fluctuations of the cortex using\u0000high-performance tracking of an array of flexible microposts adhered to\u0000multiple cultured cell types. When the confounding effects of static\u0000heterogeneity and tracking error are removed, the fluctuations are found to be\u0000heavy-tailed and well-described by a truncated L'evy stable distribution over\u0000a wide range of timescales and multiple cell types. Notably, cytoquakes appear\u0000to correspond to the largest random displacements, unifying all cortical\u0000fluctuations into a single spectrum. These findings reinforce the cortex's\u0000previously noted similarity to soft glassy materials such as foams, while the\u0000form of the fluctuation distribution will constrain future models of the\u0000cytoskeleton.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"58 32","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138511030","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}
Carlos M. Duque, Douglas M. Hall, Botond Tyukodi, Michael F. Hagan, Christian D. Santangelo, Gregory M. Grason
{"title":"Limits of economy and fidelity for programmable assembly of size-controlled triply-periodic polyhedra","authors":"Carlos M. Duque, Douglas M. Hall, Botond Tyukodi, Michael F. Hagan, Christian D. Santangelo, Gregory M. Grason","doi":"arxiv-2309.04632","DOIUrl":"https://doi.org/arxiv-2309.04632","url":null,"abstract":"We propose and investigate an extension of the Caspar-Klug symmetry\u0000principles for viral capsid assembly to the programmable assembly of\u0000size-controlled triply-periodic polyhedra, discrete variants of the Primitive,\u0000Diamond, and Gyroid cubic minimal surfaces. Inspired by a recent class of\u0000programmable DNA origami colloids, we demonstrate that the economy of design in\u0000these crystalline assemblies -- in terms of the growth of the number of\u0000distinct particle species required with the increased size-scale (e.g.\u0000periodicity) -- is comparable to viral shells. We further test the role of\u0000geometric specificity in these assemblies via dynamical assembly simulations,\u0000which show that conditions for simultaneously efficient and high-fidelity\u0000assembly require an intermediate degree of flexibility of local angles and\u0000lengths in programmed assembly. Off-target misassembly occurs via incorporation\u0000of a variant of disclination defects, generalized to the case of hyperbolic\u0000crystals. The possibility of these topological defects is a direct consequence\u0000of the very same symmetry principles that underlie the economical design,\u0000exposing a basic tradeoff between design economy and fidelity of programmable,\u0000size controlled assembly.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"58 33","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138510947","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":"Extreme first passage times for populations of identical rare events","authors":"James MacLaurin, Jay M. Newby","doi":"arxiv-2309.01827","DOIUrl":"https://doi.org/arxiv-2309.01827","url":null,"abstract":"A collection of identical and independent rare event first passage times is\u0000considered. The problem of finding the fastest out of $N$ such events to occur\u0000is called an extreme first passage time. The rare event times are singular and\u0000limit to infinity as a positive parameter scaling the noise magnitude is\u0000reduced to zero. In contrast, previous work has shown that the mean of the\u0000fastest event time goes to zero in the limit of an infinite number of walkers.\u0000The combined limit is studied. In particular, the mean time and the most likely\u0000path taken by the fastest random walker are investigated. Using techniques from\u0000large deviation theory, it is shown that there is a distinguished limit where\u0000the mean time for the fastest walker can take any positive value, depending on\u0000a single proportionality constant. Furthermore, it is shown that the mean time\u0000and most likely path can be approximated using the solution to a variational\u0000problem related to the single-walker rare event.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"52 24","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138511044","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":"Discrete-to-continuum models of pre-stressed cytoskeletal filament networks","authors":"J. Köry, N. A. Hill, X. Y. Luo, P. S. Stewart","doi":"arxiv-2309.01034","DOIUrl":"https://doi.org/arxiv-2309.01034","url":null,"abstract":"We introduce a mathematical model for the mechanical behaviour of the\u0000eukaryotic cell cytoskeleton. This discrete model involves a regular array of\u0000pre-stressed protein filaments that exhibit resistance to enthalpic stretching,\u0000joined at crosslinks to form a network. Assuming that the inter-crosslink\u0000distance is much shorter than the lengthscale of the cell, we upscale the\u0000discrete force balance to form a continuum system of governing equations and\u0000deduce the corresponding macroscopic stress tensor. We use these discrete and\u0000continuum models to analyse the imposed displacement of a bead placed in the\u0000domain, characterising the cell rheology through the force-displacement curve.\u0000We further derive an analytical approximation to the stress and strain fields\u0000in the limit of small bead radius, predicting the net force required to\u0000generate a given deformation and elucidating the dependency on the microscale\u0000properties of the filaments. We apply these models to networks of the\u0000intermediate filament vimentin and demonstrate good agreement between\u0000predictions of the discrete, continuum and analytical approaches. In\u0000particular, our model predicts that the network stiffness increases sublinearly\u0000with the filament pre-stress and scales logarithmically with the bead size.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"51 29","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138511126","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":"Learning dynamical models of single and collective cell migration: a review","authors":"David B. Brückner, Chase P. Broedersz","doi":"arxiv-2309.00545","DOIUrl":"https://doi.org/arxiv-2309.00545","url":null,"abstract":"Single and collective cell migration are fundamental processes critical for\u0000physiological phenomena ranging from embryonic development and immune response\u0000to wound healing and cancer metastasis. To understand cell migration from a\u0000physical perspective, a broad variety of models for the underlying physical\u0000mechanisms that govern cell motility have been developed. A key challenge in\u0000the development of such models is how to connect them to experimental\u0000observations, which often exhibit complex stochastic behaviours. In this\u0000review, we discuss recent advances in data-driven theoretical approaches that\u0000directly connect with experimental data to infer dynamical models of stochastic\u0000cell migration. Leveraging advances in nanofabrication, image analysis, and\u0000tracking technology, experimental studies now provide unprecedented large\u0000datasets on cellular dynamics. In parallel, theoretical efforts have been\u0000directed towards integrating such datasets into physical models from the single\u0000cell to the tissue scale with the aim of conceptualizing the emergent behavior\u0000of cells. We first review how this inference problem has been addressed in\u0000freely migrating cells on two-dimensional substrates and in structured,\u0000confining systems. Moreover, we discuss how data-driven methods can be\u0000connected with molecular mechanisms, either by integrating mechanistic\u0000bottom-up biophysical models, or by performing inference on subcellular degrees\u0000of freedom. Finally, we provide an overview of applications of data-driven\u0000modelling in developing frameworks for cell-to-cell variability in behaviours,\u0000and for learning the collective dynamics of multicellular systems.\u0000Specifically, we review inference and machine learning approaches to recover\u0000cell-cell interactions and collective dynamical modes, and how these can be\u0000integrated into physical active matter models of collective migration.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"58 46","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138510936","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":"Non-equilibrium cluster-cluster aggregation in the presence of anchoring sites","authors":"Renaud Baillou, Jonas Ranft","doi":"arxiv-2308.15162","DOIUrl":"https://doi.org/arxiv-2308.15162","url":null,"abstract":"Non-equilibrium cluster-cluster aggregation of particles diffusing in or at\u0000the cell membrane has been hypothesized to lead to domains of finite size in\u0000different biological contexts such as lipid rafts, cell adhesion complexes, or\u0000postsynaptic domains in neurons. In this scenario, the desorption of particles\u0000balances a continuous flux to the membrane, imposing a cut-off on possible\u0000aggregate sizes and giving rise to a stationary size distribution. Here, we\u0000investigate the case of non-equilibrium cluster-cluster aggregation in two\u0000dimensions where diffusing particles and/or clusters remain fixed in space at\u0000specific anchoring sites, which should be particularly relevant for synapses\u0000but may also be present in other biological or physical systems. Using an\u0000effective mean-field description of the concentration field around anchored\u0000clusters, we derive an expression for their average size as a function of\u0000parameters such as the anchoring site density. We furthermore propose and solve\u0000appropriate rate equations that allow us to predict the size distributions of\u0000both diffusing and fixed clusters. We confirm our results with particle-based\u0000simulations, and discuss potential implications for biological and physical\u0000systems.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"58 43","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138510939","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":"Applications of machine Learning to improve the efficiency and range of microbial biosynthesis: a review of state-of-art techniques","authors":"Akshay Bhalla, Suraj Rajendran","doi":"arxiv-2308.13877","DOIUrl":"https://doi.org/arxiv-2308.13877","url":null,"abstract":"In the modern world, technology is at its peak. Different avenues in\u0000programming and technology have been explored for data analysis, automation,\u0000and robotics. Machine learning is key to optimize data analysis, make accurate\u0000predictions, and hasten/improve existing functions. Thus, presently, the field\u0000of machine learning in artificial intelligence is being developed and its uses\u0000in varying fields are being explored. One field in which its uses stand out is\u0000that of microbial biosynthesis. In this paper, a comprehensive overview of the\u0000differing machine learning programs used in biosynthesis is provided, alongside\u0000brief descriptions of the fields of machine learning and microbial biosynthesis\u0000separately. This information includes past trends, modern developments, future\u0000improvements, explanations of processes, and current problems they face. Thus,\u0000this paper's main contribution is to distill developments in, and provide a\u0000holistic explanation of, 2 key fields and their applicability to improve\u0000industry/research. It also highlights challenges and research directions,\u0000acting to instigate more research and development in the growing fields.\u0000Finally, the paper aims to act as a reference for academics performing\u0000research, industry professionals improving their processes, and students\u0000looking to understand the concept of machine learning in biosynthesis.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"51 41","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138511048","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":"Genome replication in asynchronously growing microbial populations","authors":"Florian Pflug, Deepak Bhat, Simone Pigolotti","doi":"arxiv-2308.12664","DOIUrl":"https://doi.org/arxiv-2308.12664","url":null,"abstract":"Biological cells adopt specific programs to replicate their genomes.\u0000Information about the replication program of an organism can be obtained by\u0000sequencing an exponentially growing cell culture and studying the frequency of\u0000DNA fragments as a function of genomic position. However, a quantitative\u0000interpretation of this data has been challenging for asynchronously growing\u0000cultures. In this paper, we introduce a general theory to predict the abundance\u0000of DNA fragments in asynchronously growing cultures from any given stochastic\u0000model of the DNA replication program. As key examples, we present stochastic\u0000models of DNA replication in Escherichia coli and in budding yeast. In both\u0000cases, our approach leads to analytical predictions that are in excellent\u0000agreement with experimental data and permit to infer biophysically relevant\u0000parameters. In particular, our method is able to infer the locations of known\u0000replication origins in budding yeast with high accuracy. These examples\u0000demonstrate that our method can provide insight into a broad range of\u0000organisms, from bacteria to eukaryotes.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"58 48","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138510934","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}