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Physical limits on galvanotaxis depends on cell morphology and orientation 电泳的物理限制取决于细胞形态和方向
Pub Date : 2024-07-24 DOI: arxiv-2407.17420
Ifunanya Nwogbaga, Brian A. Camley
Galvanotaxis is believed to be driven by the redistribution of transmembraneproteins and other molecules, referred to as "sensors", through electrophoresisand electroosmosis. Here, we update our previous model of the limits ofgalvanotaxis due to stochasticity of sensor movements to account for cell shapeand orientation. Computing the Fisher information, we find that cells inprinciple possess more information about the electric field direction whentheir long axis is parallel to the field, but that for weak fieldsmaximum-likelihood estimators of the field direction may actually have lowervariability when the cell's long axis is perpendicular to the field. In analternate possibility, we find that if cells instead estimate the fielddirection by taking the average of all the sensor locations as its directionalcue ("vector sum"), this introduces a bias towards the short axis, an effectnot present for isotropic cells. We also explore the possibility that cellelongation arises downstream of sensor redistribution. We argue that if sensorsmigrate to the cell's rear, the cell will expand perpendicular the field - asis more commonly observed - but if sensors migrate to the front, the cell willelongate parallel to the field.
据信,通过电泳和电渗作用,跨膜蛋白和其他分子(被称为 "传感器")会重新分布,从而驱动加尔文轴向运动。在此,我们更新了之前的模型,即由于传感器运动的随机性而导致的galvanotaxis极限,以考虑细胞的形状和方向。通过计算费雪信息,我们发现当细胞长轴平行于电场时,细胞原则上拥有更多关于电场方向的信息,但对于弱电场,当细胞长轴垂直于电场时,电场方向的最大似然估计值实际上可能具有较低的变异性。在另一种可能的情况下,我们发现如果细胞将所有传感器位置的平均值作为其方向线索("矢量和")来估计场方向,就会产生偏向短轴的偏差,而各向同性细胞则不存在这种效应。我们还探讨了细胞长度在传感器重新分布下游产生的可能性。我们认为,如果传感器迁移到细胞的后部,细胞将垂直于场扩展--这是更常见的现象;但如果传感器迁移到前部,细胞将平行于场伸长。
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引用次数: 0
Understanding cell populations sharing information through the environment, as reinforcement learning 将细胞群通过环境共享信息理解为强化学习
Pub Date : 2024-07-21 DOI: arxiv-2407.15298
Masaki Kato, Tetsuya J. Kobayashi
Collective migration is a phenomenon observed in various biological systems,where the cooperation of multiple cells leads to complex functions beyondindividual capabilities, such as in immunity and development. A distinctiveexample is cell populations that not only ascend attractant gradientoriginating from targets, such as damaged tissue, but also actively modify thegradient, through their own production and degradation. While the optimality ofsingle-cell information processing has been extensively studied, the optimalityof the collective information processing that includes gradient sensing andgradient generation, remains underexplored. In this study, we formulated a cellpopulation that produces and degrades an attractant while exploring theenvironment as an agent population performing distributed reinforcementlearning. We demonstrated the existence of optimal couplings between gradientsensing and gradient generation, showing that the optimal gradient generationqualitatively differs depending on whether the gradient sensing is logarithmicor linear. The derived dynamics have a structure homogeneous to theKeller-Segel model, suggesting that cell populations might be learning.Additionally, we showed that the distributed information processing structureof the agent population enables a proportion of the population to robustlyaccumulate at the target. Our results provide a quantitative foundation forunderstanding the collective information processing mediated by attractants inextracellular environments.
集体迁移是在各种生物系统中观察到的一种现象,在这些系统中,多个细胞的合作导致了超出个体能力的复杂功能,例如在免疫和发育过程中。一个独特的例子是,细胞群不仅能从目标(如受损组织)上升吸引梯度,还能通过自身的产生和降解主动改变梯度。虽然单细胞信息处理的最优性已得到广泛研究,但包括梯度感应和梯度生成在内的集体信息处理的最优性仍未得到充分探索。在这项研究中,我们将一个在探索环境的同时产生和降解吸引子的细胞群设计为一个进行分布式强化学习的代理群。我们证明了梯度感应和梯度生成之间存在最佳耦合,并表明最佳梯度生成的定性差异取决于梯度感应是对数还是线性。此外,我们还表明,代理群体的分布式信息处理结构使得一部分群体能够在目标处稳健地积累。我们的研究结果为理解细胞外环境中由吸引子介导的集体信息处理提供了定量基础。
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引用次数: 0
Visitation Dynamics of $d$-Dimensional Fractional Brownian Motion d$维分数布朗运动的访问动力学
Pub Date : 2024-07-16 DOI: arxiv-2407.11655
L. Régnier, M. Dolgushev, O. Bénichou
The fractional Brownian motion (fBm) is a paradigmatic strongly non-Markovianprocess with broad applications in various fields. Despite their importance,the properties of the territory covered by a $d$-dimensional fBm have remainedelusive so far. Here, we study the visitation dynamics of the fBm byconsidering the time $tau_n$ required to visit a site, defined as a unit cellof a $d$-dimensional lattice, when $n$ sites have been visited. Relying onscaling arguments, we determine all temporal regimes of the probabilitydistribution function of $tau_n$. These results are confirmed by extensivenumerical simulations that employ large-deviation Monte Carlo algorithms.Besides these theoretical aspects, our results account for the tracking data oftelomeres in the nucleus of mammalian cells, microspheres in an agorose gel,and vacuoles in the amoeba, which are experimental realizations of fBm.
分数布朗运动(fBm)是一种典型的强非马尔可夫过程,在各个领域都有广泛的应用。尽管其重要性不言而喻,但迄今为止,关于 $d$ 维 fBm 所覆盖区域的特性仍是个未知数。在这里,我们通过考虑访问一个站点所需的时间 $tau_n$来研究 fBm 的访问动力学,该站点被定义为 $d$ 维网格的一个单元单元,当 $n$ 站点被访问时。根据缩放参数,我们确定了 $tau_n$ 的概率分布函数的所有时间状态。除了这些理论方面,我们的结果还解释了哺乳动物细胞核中的球体、琼脂糖凝胶中的微球和变形虫中的空泡的跟踪数据,这些都是 fBm 的实验实现。
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引用次数: 0
A Primitive Model for Predicting Membrane Currents in Excitable Cells Based Only on Ion Diffusion Coefficients 仅根据离子扩散系数预测可兴奋细胞膜电流的原始模型
Pub Date : 2024-07-12 DOI: arxiv-2407.09474
Vivaan Patel, Joshua D. Priosoetanto, Aashutosh Mistry, John Newman, Nitash P. Balsara
Classical models for predicting current flow in excitable cells such asaxons, originally proposed by Hodgkin and Huxley, rely on empiricalvoltage-gating parameters that quantify ion transport across sodium andpotassium ion channels. We propose a primitive model for predicting thesecurrents based entirely on well-established ion diffusion coefficients. Changesinside the excitable cell due to the opening of a central sodium channel areconfined to a growing hemisphere with a radius that is governed by the sodiumion diffusion coefficient. The sodium channel, which is open throughout thecalculation, activates and deactivates naturally due to coupledelectrodiffusion processes. The characteristic time of current pulses, whichare in the picoampere range, increases from 10$^{-5}$ to 10$^{-1}$ s as channeldensity is decreased from 10,000 to 1 channel per micrometer squared. Modelpredictions are compared with data obtained from giant squid axons withoutinvoking any gating parameters.
最初由霍奇金和赫胥黎提出的用于预测诸如轴突等可兴奋细胞中电流流动的经典模型,依赖于量化钠离子和钾离子通道中离子传输的经验电压-门控参数。我们提出了一个完全基于成熟的离子扩散系数来预测这些电流的原始模型。由于中心钠离子通道的开放,可兴奋细胞内的变化被限制在一个半径不断扩大的半球内,其半径由钠离子扩散系数决定。钠通道在整个计算过程中处于开放状态,由于耦合电扩散过程而自然激活和失活。当通道密度从每平方微米 10,000 个通道降低到 1 个通道时,电流脉冲的特征时间从 10$^{-5}$ 秒增加到 10$^{-1}$ 秒,其范围为皮安培。将模型预测结果与从巨鱿轴突获得的数据进行了比较,后者没有调用任何门控参数。
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引用次数: 0
E. coli do not count single molecules 大肠杆菌不计算单个分子
Pub Date : 2024-07-09 DOI: arxiv-2407.07264
Henry H. Mattingly, Keita Kamino, Jude Ong, Rafaela Kottou, Thierry Emonet, Benjamin B. Machta
Organisms must perform sensory-motor behaviors to survive. What bounds orconstraints limit behavioral performance? Previously, we found that thegradient-climbing speed of a chemotaxing Escherichia coli is near a bound setby the limited information they acquire from their chemical environments. Herewe ask what limits their sensory accuracy. Past theoretical analyses have shownthat the stochasticity of single molecule arrivals sets a fundamental limit onthe precision of chemical sensing. Although it has been argued that bacteriaapproach this limit, direct evidence is lacking. Here, using information theoryand quantitative experiments, we find that E. coli's chemosensing is notlimited by the physics of particle counting. First, we derive the physicallimit on the behaviorally-relevant information that any sensor can get about achanging chemical concentration, assuming that every molecule arriving at thesensor is recorded. Then, we derive and measure how much information E. coli'ssignaling pathway encodes during chemotaxis. We find that E. coli encode twoorders of magnitude less information than an ideal sensor limited only by shotnoise in particle arrivals. These results strongly suggest that constraintsother than particle arrival noise limit E. coli's sensory fidelity.
生物必须进行感官运动行为才能生存。是什么界限或约束限制了行为表现?之前,我们发现大肠杆菌的化学趋向爬行速度接近它们从化学环境中获取的有限信息所设定的界限。在此,我们想知道是什么限制了它们的感官准确性。过去的理论分析表明,单分子到达的随机性为化学感应的精确性设定了基本限制。尽管有人认为细菌已经接近了这一极限,但却缺乏直接证据。在这里,我们利用信息论和定量实验发现,大肠杆菌的化学传感不受粒子计数物理学的限制。首先,我们推导出了任何传感器所能获得的有关化学浓度变化的行为相关信息的物理极限,假设每一个到达传感器的分子都被记录下来。然后,我们推导并测量了大肠杆菌信号通路在趋化过程中编码的信息量。我们发现,与理想的传感器相比,大肠杆菌编码的信息量要少两个数量级,而理想的传感器只受到粒子到达时的镜头噪声的限制。这些结果有力地表明,除了粒子到达噪声之外,还有其他因素限制了大肠杆菌的感官保真度。
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引用次数: 0
Engineering morphogenesis of cell clusters with differentiable programming 利用可分化程序设计细胞簇的形态发生
Pub Date : 2024-07-08 DOI: arxiv-2407.06295
Ramya Deshpande, Francesco Mottes, Ariana-Dalia Vlad, Michael P. Brenner, Alma dal Co
Understanding the rules underlying organismal development is a major unsolvedproblem in biology. Each cell in a developing organism responds to signals inits local environment by dividing, excreting, consuming, or reorganizing, yethow these individual actions coordinate over a macroscopic number of cells togrow complex structures with exquisite functionality is unknown. Here we userecent advances in automatic differentiation to discover local interactionrules and genetic networks that yield emergent, systems-level characteristicsin a model of development. We consider a growing tissue with cellularinteractions are mediated by morphogen diffusion, differential cell adhesionand mechanical stress. Each cell has an internal genetic network that it usesto make decisions based on its local environment. We show that one cansimultaneously learn parameters governing the cell interactions and the geneticnetwork for complex developmental scenarios, including the symmetry breaking ofan embryo from an initial cell, the creation of emergent chemicalgradients,homogenization of growth via mechanical stress, programmed growthinto a prespecified shape, and the ability to repair from damage. When combinedwith recent experimental advances measuring spatio-temporal dynamics and geneexpression of cells in a growing tissue, the methodology outlined here offers apromising path to unravelling the cellular basis of development.
了解生物体发育的基本规律是生物学中一个尚未解决的重大问题。正在发育的生物体中的每个细胞都会通过分裂、排泄、消耗或重组等方式对其局部环境中的信号做出反应,但这些个体行为如何在数量庞大的细胞中相互协调,从而生长出具有精巧功能的复杂结构,目前还不得而知。在这里,我们利用自动分化技术的最新进展,在一个发育模型中发现了产生突发性系统级特征的局部相互作用规则和遗传网络。我们考虑了一个生长中的组织,其细胞相互作用由形态发生扩散、不同细胞粘附和机械应力介导。每个细胞都有一个内部遗传网络,用于根据局部环境做出决策。我们的研究表明,在复杂的发育过程中,人们可以同时学习细胞相互作用和遗传网络的参数,包括从初始细胞打破胚胎的对称性、创造新出现的化学梯度、通过机械应力使生长均匀化、按程序生长成预先指定的形状,以及从损伤中修复的能力。结合最近测量生长组织中细胞时空动态和基因表达的实验进展,本文概述的方法为揭示发育的细胞基础提供了一条光明大道。
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引用次数: 0
Feeders and Expellers, Two Types of Animalcules With Outboard Cilia, Have Distinct Surface Interactions 进食者和排泄者这两种具有外向纤毛的动物分子具有不同的表面相互作用
Pub Date : 2024-06-29 DOI: arxiv-2407.00439
Praneet Prakash, Marco Vona, Raymond E. Goldstein
Within biological fluid dynamics, it is conventional to distinguish between"puller" and "pusher" microswimmers on the basis of the forward or aft locationof the flagella relative to the cell body: typically, bacteria are pushers andalgae are pullers. Here we note that since many pullers have "outboard" ciliaor flagella displaced laterally from the cell centerline on both sides of theorganism, there are two important subclasses whose far-field is that of astresslet, but whose near field is qualitatively more complex. The ciliary beatcreates not only a propulsive force but also swirling flows that can berepresented by paired rotlets with two possible senses of rotation, either"feeders" that sweep fluid toward the cell apex, or "expellers" that push fluidaway. Experimental studies of the rotifer $Brachionus~plicatilis$ incombination with earlier work on the green algae $Chlamydomonas~reinhardtii$show that the two classes have markedly different interactions with surfaces.When swimming near a surface, expellers such as $C.~reinhardtii$ scatter fromthe wall, whereas a feeder like $B.~plicatilis$ stably attaches. This resultsin a stochastic "run-and-stick" locomotion, with periods of ballistic motionparallel to the surface interrupted by trapping at the surface.
在生物流体力学中,传统的做法是根据鞭毛相对于细胞体的前后位置来区分 "拉动者 "和 "推动者":通常,细菌是推动者,藻类是拉动者。在这里,我们注意到,由于许多拉动者的纤毛或鞭毛从细胞中心线向两侧偏移,因此有两个重要的亚类,它们的远场与纤毛虫相同,但近场在质量上更为复杂。纤毛搏动不仅能产生推动力,还能产生漩涡流,这种漩涡流可以用成对的小转子来表示,小转子有两种可能的旋转方式,一种是将流体扫向细胞顶点的 "喂食器",另一种是将流体推开的 "驱逐器"。对轮虫($Brachionus~plicatilis$)的实验研究以及早先对绿藻($Chlamydomonas~reinhardtii$)的研究表明,这两类轮虫与表面的相互作用明显不同。这导致了一种随机的 "奔跑-粘附 "运动,在与表面平行的弹道运动期间,被困在表面的运动被打断。
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引用次数: 0
High Throughput Parameter Estimation and Uncertainty Analysis Applied to the Production of Mycoprotein from Synthetic Lignocellulosic Hydrolysates 高通量参数估计和不确定性分析在利用合成木质纤维素水解物生产菌体蛋白中的应用
Pub Date : 2024-06-28 DOI: arxiv-2407.00209
Mason Banks, Mark Taylor, Miao Guo
The current global food system produces substantial waste and carbonemissions while exacerbating the effects of global hunger and proteindeficiency. This study aims to address these challenges by exploring the use oflignocellulosic agricultural residues as feedstocks for microbial proteinfermentation, focusing on Fusarium venenatum A3/5, a mycelial strain known forits high protein yield and quality. We propose a high throughput microlitrebatch fermentation system paired with analytical chemistry to generatetime-series data of microbial growth and substrate utilisation. An unstructuredbiokinetic model was developed using a bootstrap sampling approach to quantifyuncertainty in the parameter estimates. The model was validated against anindependent dataset of a different glucose-xylose composition to assess thepredictive performance. Our results indicate a robust model fit with highcoefficients of determination and low root mean squared errors for biomass,glucose, and xylose concentrations. Estimated parameter values providedinsights into the resource utilisation strategies of Fusarium venenatum A3/5 inmixed substrate cultures, aligning well with previous research findings.Significant correlations between estimated parameters were observed,highlighting challenges in parameter identifiability. This work provides afoundational model for optimising the production of microbial protein fromlignocellulosic waste, contributing to a more sustainable global food system.
当前的全球粮食系统产生了大量废物和碳排放,同时加剧了全球饥饿和蛋白质缺乏的影响。本研究旨在通过探索利用木质纤维素农作物残留物作为微生物蛋白质发酵的原料来应对这些挑战,研究重点是Fusarium venenatum A3/5,这是一种以蛋白质产量高、质量好而著称的菌丝菌株。我们提出了一种高通量微升批量发酵系统,该系统与分析化学相结合,可生成微生物生长和底物利用的时间序列数据。我们利用引导取样法建立了一个非结构化生物动力学模型,以量化参数估计的不确定性。该模型通过不同葡萄糖-木糖组成的独立数据集进行了验证,以评估其预测性能。结果表明,模型拟合稳健,生物量、葡萄糖和木糖浓度的决定系数高,均方根误差小。估计的参数值提供了对混合基质培养液中文镰刀菌 A3/5 资源利用策略的见解,与之前的研究结果非常吻合。这项工作为优化利用木质纤维素废物生产微生物蛋白质提供了一个基础模型,有助于建立一个更具可持续性的全球粮食系统。
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引用次数: 0
Statistical description of mobile oscillators in embryonic pattern formation 胚胎模式形成过程中移动振荡器的统计描述
Pub Date : 2024-06-16 DOI: arxiv-2406.10936
Koichiro Uriu, Luis G. Morelli
Synchronization of mobile oscillators occurs in numerous contexts, includingphysical, chemical, biological and engineered systems. In vertebrate embryonicdevelopment, a segmental body structure is generated by a population of mobileoscillators. Cells in this population produce autonomous gene expressionrhythms, and interact with their neighbors through local signaling. These cellsform an extended tissue where frequency and cell mobility gradients coexist.Gene expression kinematic waves travel through this tissue and pattern thesegment boundaries. It has been shown that oscillator mobility promotes globalsynchronization. However, in vertebrate segment formation, mobility may alsointroduce local fluctuations in kinematic waves and impair segment boundaries.Here we derive a general framework for mobile oscillators that relates localmobility fluctuations to synchronization dynamics and pattern robustness. Weformulate a statistical description of mobile phase oscillators in terms of aprobability density. We obtain and solve diffusion equations for the averagephase and variance, revealing the relationship between local fluctuations andglobal synchronization in a homogeneous population of oscillators. Analysis ofthe probability density for large mobility identifies a mean-field transition,where locally coupled oscillators start behaving as if each oscillator wascoupled with all the others. We extend the statistical description toinhomogeneous systems to address the gradients present in the vertebratesegmenting tissue. The theory relates pattern stability to mobility, couplingand pattern wavelength. The general approach of the statistical description maybe applied to mobile oscillators in other contexts, as well as to otherpatterning systems where mobility is present.
移动振子的同步发生在许多情况下,包括物理、化学、生物和工程系统。在脊椎动物的胚胎发育过程中,身体的节段结构是由一群移动振子产生的。该群体中的细胞产生自主的基因表达节律,并通过局部信号与邻近细胞相互作用。这些细胞形成了一个扩展组织,在这个组织中,频率梯度和细胞移动梯度并存。基因表达运动波穿过这个组织,并将这些节段边界模式化。研究表明,振荡器的流动性促进了全球同步。然而,在脊椎动物的节段形成过程中,流动性也可能带来运动波的局部波动,并损害节段边界。在这里,我们推导出了一个流动振荡器的总体框架,它将局部流动性波动与同步动力学和模式稳健性联系起来。我们用概率密度对移动相位振荡器进行了统计描述。我们获得并求解了平均相位和方差的扩散方程,揭示了同质振荡器群体中局部波动与全局同步之间的关系。对大流动性概率密度的分析确定了平均场转换,在这种转换中,局部耦合振荡器开始表现得就像每个振荡器都与其他所有振荡器耦合一样。我们将统计描述扩展到均质系统中,以解决脊椎动物分割组织中存在的梯度问题。该理论将模式稳定性与流动性、耦合和模式波长联系起来。统计描述的一般方法可能适用于其他情况下的移动振荡器,以及存在移动性的其他图案系统。
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引用次数: 0
Collective Invasion: When does domain curvature matter? 集体入侵:域曲率何时重要?
Pub Date : 2024-06-12 DOI: arxiv-2406.08291
Joseph J. Pollacco, Ruth E. Baker, Philip K. Maini
Real-world cellular invasion processes often take place in curved geometries.Such problems are frequently simplified in models to neglect the curvedgeometry in favour of computational simplicity, yet doing so risks inaccuracyin any model-based predictions. To quantify the conditions under whichneglecting a curved geometry are justifiable, we examined solutions to theFisher-Kolmogorov-Petrovsky-Piskunov (Fisher-KPP) model, a paradigm nonlinearreaction-diffusion equation typically used to model spatial invasion, on anannular geometry. Defining $epsilon$ as the ratio of the annulus thickness$delta$ and radius $r_0$ we derive, through an asymptotic expansion, theconditions under which it is appropriate to ignore the domain curvature, aresult that generalises to other reaction-diffusion equations with constantdiffusion coefficient. We further characterise the nature of the solutionsthrough numerical simulation for different $r_0$ and $delta$. Thus, wequantify the size of the deviation from an analogous simulation on therectangle, and how this deviation changes across the width of the annulus. Ourresults grant insight into when it is appropriate to neglect the domaincurvature in studying travelling wave behaviour in reaction-diffusionequations.
现实世界中的细胞侵袭过程往往发生在弯曲的几何形状中。为了简化计算,这类问题经常被简化成忽略弯曲几何形状的模型,但这样做有可能导致任何基于模型的预测不准确。为了量化在什么条件下忽略弯曲几何是合理的,我们研究了Fisher-Kolmogorov-Petrovsky-Piskunov(Fisher-KPP)模型在环状几何上的解,这是一个典型的非线性反应-扩散方程,通常用于模拟空间入侵。将 $epsilon$ 定义为环形厚度 $delta$ 与半径 $r_0$ 的比值,我们通过渐近展开推导出在哪些条件下适合忽略域曲率,这一结果可推广到其他具有恒定扩散系数的反应扩散方程。我们通过数值模拟进一步描述了不同 $r_0$ 和 $delta$ 的解的性质。因此,我们量化了与该角上类似模拟的偏差大小,以及这种偏差在环面宽度上的变化情况。我们的结果让我们了解到,在研究反应扩散方程中的行波行为时,何时忽略域曲率是合适的。
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引用次数: 0
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arXiv - QuanBio - Cell Behavior
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