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Allosteric communication mediated by protein contact clusters: A dynamical model 由蛋白质接触簇介导的异构通讯:动力学模型
Pub Date : 2024-08-27 DOI: arxiv-2408.15110
Ahmed A. A. I. Ali, Emanuel Dorbath, Gerhard Stock
Allostery refers to the puzzling phenomenon of long-range communicationbetween distant sites in proteins. Despite its importance in biomolecularregulation and signal transduction, the underlying dynamical process is notwell understood. This study introduces a dynamical model of allostericcommunication based on "contact clusters"-localized groups of highly correlatedcontacts that facilitate interactions between secondary structures. The modelshows that allostery involves a multi-step process with cooperative contactchanges within clusters and communication between distant clusters mediated byrigid secondary structures. Considering time-dependent experiments on aphotoswitchable PDZ3 domain, extensive (in total $sim 500,mu$s) moleculardynamics simulations are conducted that directly monitor the photoinducedallosteric transition. The structural reorganization is illustrated by the timeevolution of the contact clusters and the ligand, which affects the nonlocalcoupling between distant clusters. A timescale analysis reveals dynamics fromnano- to microseconds, which are in excellent agreement with the experimentallymeasured timescales.
异构指的是蛋白质中遥远位点之间的长程通讯这一令人费解的现象。尽管这种现象在生物分子调控和信号转导中非常重要,但人们对其背后的动态过程却不甚了解。本研究介绍了一种基于 "接触集群 "的异构通讯动力学模型--高度相关的接触的局部集群可促进二级结构之间的相互作用。该模型显示,异构涉及一个多步骤过程,其中包括簇内的合作性接触变化和由刚性二级结构介导的远距离簇间的交流。考虑到对可光照开关的 PDZ3 结构域进行的时间依赖性实验,我们进行了大量(总计 500 次)分子动力学模拟,直接监测光照诱导的异质转变。接触簇和配体的时间演变说明了结构重组,这影响了远距离簇之间的非局部耦合。时间尺度分析显示了从纳秒到微秒的动态变化,这与实验测量的时间尺度非常吻合。
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引用次数: 0
Closed-loop control of active nematic flows 主动向列流动的闭环控制
Pub Date : 2024-08-26 DOI: arxiv-2408.14414
Katsu Nishiyama, John Berezney, Michael M. Norton, Akshit Aggarwal, Saptorshi Ghosh, Michael F. Hagan, Zvonimir Dogic, Seth Fraden
Living things enact control of non-equilibrium, dynamical structures throughcomplex biochemical networks, accomplishing spatiotemporally-orchestratedphysiological tasks such as cell division, motility, and embryogenesis. Whilethe exact minimal mechanisms needed to replicate these behaviors usingsynthetic active materials are unknown, controlling the complex, often chaotic,dynamics of active materials is essential to their implementation as engineeredlife-like materials. Here, we demonstrate the use of external feedback controlto regulate and control the spatially-averaged speed of a model active materialwith time-varying actuation through applied light. We systematically vary thecontroller parameters to analyze the steady-state flow speed and temporalfluctuations, finding the experimental results in excellent agreement withpredictions from both a minimal coarse-grained model and fullnematohydrodynamic simulations. Our findings demonstrate thatproportional-integral control can effectively regulate the dynamics of activenematics in light of challenges posed by the constituents, such as sampleaging, protein aggregation, and sample-to-sample variability. As in livingthings, deviations of active materials from their steady-state behavior canarise from internal processes and we quantify the important consequences ofthis coupling on the controlled behavior of the active nematic. Finally, theinteraction between the controller and the intrinsic timescales of the activematerial can induce oscillatory behaviors in a regime of parameter space thatqualitatively matches predictions from our model. This work underscores thepotential of feedback control in manipulating the complex dynamics of activematter, paving the way for more sophisticated control strategies in the designof responsive, life-like materials.
生物通过复杂的生化网络对非平衡态动态结构进行控制,完成时空协调的生理任务,如细胞分裂、运动和胚胎发育。虽然利用合成活性材料复制这些行为所需的最小精确机制尚不清楚,但控制活性材料的复杂(通常是混沌)动力学对其作为类生命工程材料的实现至关重要。在这里,我们展示了利用外部反馈控制来调节和控制模型活性材料的空间平均速度,并通过施加光进行时变驱动。我们系统地改变了控制器参数,分析了稳态流速和时间波动,发现实验结果与最小粗粒度模型和全流体力学模拟的预测结果非常一致。我们的研究结果表明,比例积分控制可以有效地调节活动动力学的动态变化,以应对样本老化、蛋白质聚集和样本间变异性等成分带来的挑战。与生命体一样,活性材料偏离其稳态行为可能源于内部过程,我们量化了这种耦合对活性向列控制行为的重要影响。最后,控制器与活性材料固有时间尺度之间的相互作用会在参数空间的某一范围内诱发振荡行为,而这一范围与我们模型的预测结果基本吻合。这项研究强调了反馈控制在操纵活性物质复杂动力学方面的潜力,为设计反应灵敏、栩栩如生的材料时采用更复杂的控制策略铺平了道路。
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引用次数: 0
Peptide Classification from Statistical Analysis of Nanopore Translocation Experiments 通过对纳米孔转位实验的统计分析进行多肽分类
Pub Date : 2024-08-26 DOI: arxiv-2408.14275
Julian Hoßbach, Samuel Tovey, Tobias Ensslen, Jan C. Behrends, Christian Holm
Protein characterization using nanopore-based devices promises to be abreakthrough method in basic research, diagnostics, and analytics. Currentresearch includes the use of machine learning to achieve this task. In thiswork, a comprehensive statistical analysis of nanopore current signals isperformed and demonstrated to be sufficient for classifying up to 42 peptideswith 70 % accuracy. Two sets of features, the statistical moments and thecatch22 set, are compared both in their representations and after trainingsmall classifier neural networks. We demonstrate that complex features of theevents, captured in both the catch22 set and the central moments, are key inclassifying peptides with otherwise similar mean currents. These resultshighlight the efficacy of purely statistical analysis of nanopore data andsuggest a path forward for more sophisticated classification techniques.
使用基于纳米孔的设备进行蛋白质表征有望成为基础研究、诊断和分析领域的突破性方法。目前的研究包括使用机器学习来完成这项任务。在这项工作中,对纳米孔电流信号进行了全面的统计分析,结果表明足以对多达 42 种肽进行分类,准确率高达 70%。我们比较了两组特征,即统计矩(statistical moments)和捕获集(catch22 set),这两组特征的表现形式和训练小型分类器神经网络后的结果。我们证明,catch22 集和中心矩捕捉到的事件复杂特征是对具有相似平均电流的肽进行分类的关键。这些结果凸显了对纳米孔数据进行纯统计分析的功效,并为更复杂的分类技术指明了前进的道路。
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引用次数: 0
Easy-Plane Alignment of Anisotropic Biofluid Crystals in a Magnetic Field: Implications for Rod Orientation 磁场中各向异性生物流体晶体的易平面排列:磁棒定向的意义
Pub Date : 2024-08-25 DOI: arxiv-2408.13946
Robert J. Deissler, Robert Brown
We study the orientation in a uniform magnetic field of rod-like anisotropicbiofluid crystals with an easy plane that makes an oblique angle with thecrystal's c-axis. For a sufficiently strong field, these crystalline rodsorient themselves such that the crystal's easy plane is parallel to themagnetic field, the rod's direction being defined as the direction of thecrystal's c-axis. As the rod rotates about the crystal's hard axis there willtherefore be a range of angles that the rod makes with the magnetic field. Wedetail this behavior by first providing illustrations of hemozoin crystals atvarious orientations. These illustrations clearly demonstrate that theorientation angle that the crystalline rod makes with respect to the magneticfield varies from about 30 deg to 150 deg. We also derive an analyticalexpression for the probability density function for the orientation angle. Wefind that the orientation angles are not uniformly distributed between thelimits of 30 deg and 150 deg, but rather tend to cluster near these limits.This suggests experimental tests and addresses confusion about the rodorientation found in past literature. The relevance to other anisotropicbiofluid crystals, such as those produced by gout, is also discussed.
我们研究了棒状各向异性生物流体晶体在均匀磁场中的取向,这些晶体的易平面与晶体的 c 轴成斜角。在足够强的磁场中,这些晶体棒会自行定向,使晶体的易平面与磁场平行,棒的方向被定义为晶体 c 轴的方向。因此,当棒围绕晶体的硬轴旋转时,棒与磁场会形成一定的角度范围。我们首先提供了不同方向的血安息香晶体的插图,以此来说明这种行为。这些插图清楚地表明,晶棒相对于磁场的取向角度从 30 度到 150 度不等。我们还推导出了取向角概率密度函数的分析表达式。我们发现取向角并不是均匀分布在 30 度和 150 度这两个极限之间,而是倾向于聚集在这些极限附近。我们还讨论了与其他各向异性生物流体晶体(如痛风产生的晶体)的相关性。
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引用次数: 0
Thermodynamics for Reduced Models of Breakable Amyloid Filaments Based on Maximum Entropy Principle 基于最大熵原理的可断裂淀粉样蛋白丝还原模型热力学
Pub Date : 2024-08-25 DOI: arxiv-2409.05881
Xinyu Zhang, Haiyang Jia, Wuyue Yang, Liangrong Peng, Liu Hong
Amyloid filaments are associated with neurodegenerative diseases such asAlzheimer's and Parkinson's. Simplified models of amyloid aggregation arecrucial because the original mass-action equations involve numerous variables,complicating analysis and understanding. While dynamical aspects of simplifiedmodels have been widely studied, their thermodynamic properties are lessunderstood. In this study, we explore the Maximum Entropy Principle(MEP)-reduced models, initially developed for dynamical analysis, from abrand-new thermodynamic perspective. Analytical expressions along withnumerical simulations demonstrate that the discrete MEP-reduced model strictlyretains laws of thermodynamics, which holds true even when filament lengthstransit from discrete values to continuous real numbers. Our findings not onlyclarify the thermodynamic consistency between the MEP-reduced models and theoriginal models of amyloid filaments for the first time, but also suggestavenues for future research into the model-reduction thermodynamics.
淀粉样蛋白丝与神经退行性疾病(如阿尔茨海默氏症和帕金森氏症)有关。淀粉样蛋白聚集的简化模型至关重要,因为原始的质量-作用方程涉及众多变量,使分析和理解复杂化。虽然简化模型的动力学方面已被广泛研究,但对其热力学特性的了解却较少。在本研究中,我们从全新的热力学角度探讨了最初为动力学分析而开发的最大熵原理(MEP)简化模型。分析表达式和数值模拟证明,离散的 MEP 还原模型严格遵守热力学定律,即使当丝的长度从离散值转变为连续实数时也是如此。我们的发现不仅首次阐明了 MEP 还原模型与淀粉样蛋白丝原始模型之间的热力学一致性,而且为未来研究模型还原热力学提供了线索。
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引用次数: 0
Giant enhancement of bacterial upstream swimming in macromolecular flows 细菌在大分子流中逆流而上的巨大增强效应
Pub Date : 2024-08-25 DOI: arxiv-2408.13694
Ding Cao, Ran Tao, Albane Théry, Song Liu, Arnold J. T. M. Mathijssen, Yilin Wu
Many bacteria live in natural and clinical environments with abundantmacromolecular polymers. Macromolecular fluids commonly display viscoelasticityand non-Newtonian rheological behavior; it is unclear how these complex-fluidproperties affect bacterial transport in flows. Here we combine high-resolutionmicroscopy and numerical simulations to study bacterial response to shear flowsof various macromolecular fluids. In stark contrast to the case in Newtonianshear flows, we found that flagellated bacteria in macromolecular flows displaya giant capacity of upstream swimming (a behavior resembling fish swimmingagainst current) near solid surfaces: The cells can counteract flow washing atshear rates up to ~65 $s^{-1}$, one order of magnitude higher than the limitfor cells swimming in Newtonian flows. The significant enhancement of upstreamswimming depends on two characteristic complex-fluid properties, namelyviscoelasticity and shear-thinning viscosity; meanwhile, increasing theviscosity with a Newtonian polymer can prevent upstream motion. By visualizingflagellar bundles and modeling bacterial swimming in complex fluids, we explainthe phenomenon as primarily arising from the augmentation of a "weathervaneeffect" in macromolecular flows due to the presence of a viscoelastic liftforce and a shear-thinning induced azimuthal torque promoting the alignment ofbacteria against the flow direction. Our findings shed light on bacterialtransport and surface colonization in macromolecular environments, and mayinform the design of artificial helical microswimmers for biomedicalapplications in physiological conditions.
许多细菌生活在大分子聚合物丰富的自然和临床环境中。大分子流体通常具有粘弹性和非牛顿流变行为;目前还不清楚这些复杂的流体特性如何影响细菌在流体中的迁移。在这里,我们结合高分辨率显微镜和数值模拟来研究细菌对各种高分子流体剪切流的反应。与牛顿剪切流中的情况形成鲜明对比的是,我们发现高分子流中的鞭毛细菌在固体表面附近显示出巨大的逆流游动能力(类似于鱼类逆流游动的行为):细胞在剪切速率高达~65 s^{-1}$的情况下可以抵消水流冲刷,比细胞在牛顿流中游动的极限高出一个数量级。上游游动能力的显著增强取决于两种复杂流体的特性,即粘弹性和剪切稀化粘度;同时,用牛顿聚合物增加粘度可以阻止上游运动。通过对扇形束的可视化和复杂流体中细菌游动的建模,我们解释了这一现象主要源于大分子流中 "风向标效应 "的增强,这是由于粘弹性提升力和剪切稀化诱导的方位角力矩的存在促进了细菌逆流向排列。我们的发现揭示了细菌在大分子环境中的迁移和表面定植,并为设计生理条件下生物医学应用的人工螺旋微泳道提供了参考。
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引用次数: 0
Thermodynamic inference of correlations in nonequilibrium collective dynamics 非平衡集体动力学中相关性的热力学推断
Pub Date : 2024-08-23 DOI: arxiv-2408.13026
Michalis Chatzittofi, Ramin Golestanian, Jaime Agudo-Canalejo
The theory of stochastic thermodynamics has revealed many useful fluctuationrelations, with the thermodynamic uncertainty relation (TUR) being a theorem ofmajor interest. When many nonequilibrium currents interact with each other, anaive application of the TUR to an individual current can result in an apparentviolation of the TUR bound. Here, we explore how such an apparent violation canbe used to put a lower bound on the strength of correlations as well as thenumber of interacting currents in collective dynamics. Our proposed protocolallows for the inference of hidden correlations in experiment, for example whena team of molecular motors pulls on the same cargo but only one or a subset ofthem is fluorescently tagged. By solving analytically and numerically severalmodels of many-body nonequilibrium dynamics, we ascertain under whichconditions this strategy can be applied and the inferred bound on correlationsbecomes tight.
随机热力学理论揭示了许多有用的波动关系,其中热力学不确定性关系(TUR)是人们最感兴趣的一个定理。当许多非平衡电流相互作用时,对单个电流直接应用热力学不确定性关系会导致对热力学不确定性关系约束的明显违反。在这里,我们探讨了如何利用这种表面违反来降低相关性的强度以及集体动力学中相互作用电流的数量。我们提出的协议允许在实验中推断隐藏的相关性,例如,当一组分子马达拉动相同的货物,但其中只有一个或一个子集被荧光标记时。通过分析和数值求解多体非平衡动力学的几个模型,我们确定了在哪些条件下可以应用这种策略,并且推断出的相关性约束变得紧密。
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引用次数: 0
Protein overabundance is driven by growth robustness 蛋白质过剩是生长稳健性的驱动因素
Pub Date : 2024-08-21 DOI: arxiv-2408.11952
H. James Choi, Teresa W. Lo, Kevin J. Cutler, Dean Huang, W. Ryan Will, Paul A. Wiggins
Protein expression levels optimize cell fitness: Too low an expression levelof essential proteins will slow growth by compromising essential processes;whereas overexpression slows growth by increasing the metabolic load. Thistrade-off naively predicts that cells maximize their fitness by sufficiency,expressing just enough of each essential protein for function. We test thisprediction in the naturally-competent bacterium Acinetobacter baylyi bycharacterizing the proliferation dynamics of essential-gene knockouts at asingle-cell scale (by imaging) as well as at a genome-wide scale (by TFNseq).In these experiments, cells proliferate for multiple generations as targetprotein levels are diluted from their endogenous levels. This approachfacilitates a proteome-scale analysis of protein overabundance. As predicted bythe Robustness-Load Trade-Off (RLTO) model, we find that roughly 70% ofessential proteins are overabundant and that overabundance increases as theexpression level decreases, the signature prediction of the model. Theseresults reveal that robustness plays a fundamental role in determining theexpression levels of essential genes and that overabundance is a key mechanismfor ensuring robust growth.
蛋白质表达水平可优化细胞的适应性:必需蛋白表达量过低,会影响基本过程,从而减缓生长速度;而表达量过大,则会增加代谢负荷,从而减缓生长速度。这种权衡天真地预测,细胞会通过表达足够的每种必需蛋白来实现其功能的最大化。在这些实验中,当目标蛋白水平从内源水平稀释时,细胞会增殖多代。在这些实验中,细胞会增殖多代,目标蛋白水平会从内源水平被稀释。这种方法有助于在蛋白质组范围内分析蛋白质过量。正如稳健性-负载权衡(RLTO)模型所预测的那样,我们发现大约 70% 的重要蛋白质过量表达,而且随着表达水平的降低,过量表达的程度也在增加,这正是该模型的特征性预测。这些结果表明,稳健性在决定重要基因的表达水平方面起着根本性的作用,而过量表达是确保稳健生长的关键机制。
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引用次数: 0
Effects of curvature on growing films of microorganisms 曲率对微生物生长膜的影响
Pub Date : 2024-08-21 DOI: arxiv-2408.11581
Yuta Kuroda, Takeshi Kawasaki, Andreas M. Menzel
To provide insight into the basic properties of emerging structures whenbacteria or other microorganisms conquer surfaces, it is crucial to analyzetheir growth behavior during the formation of thin films. In this regard, manytheoretical studies focus on the behavior of elongating straight objects. Theyrepel each other through volume exclusion and divide into two halves whenreaching a certain threshold length. However, in reality, hardly any object ofa certain elongation is perfectly straight. Therefore, we here study theconsequences of curvature on the growth of colonies and thin active films. Agiven amount of curvature is prescribed to each growing individual.Particularly, we analyze how this individual curvature affects the size oforientationally ordered domains in the colony and find a significant decrease.Instead, strings of stacked curved cells emerge that show branched structures.Furthermore, we identify a significant spatio-orientational coupling that isnot observed in colonies of straight cells. Our results are important for afundamental understanding of the interaction and spreading of microorganisms onsurfaces, with implications for medical applications and bioengineering.
为了深入了解细菌或其他微生物征服表面时产生的新结构的基本特性,分析它们在薄膜形成过程中的生长行为至关重要。在这方面,许多理论研究都侧重于拉长的直线物体的行为。它们通过体积排斥相互排斥,并在达到某个临界长度时分成两半。然而,在现实中,几乎没有一个具有一定伸长率的物体是完全笔直的。因此,我们在此研究曲率对菌落和活性薄膜生长的影响。特别是,我们分析了这种个体曲率如何影响菌落中定向有序结构域的大小,结果发现这种影响显著减小,相反,堆叠的弯曲细胞串出现了分枝结构。我们的研究结果对于从根本上理解微生物在表面上的相互作用和传播非常重要,对医疗应用和生物工程具有重要意义。
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引用次数: 0
Motor-driven microtubule diffusion in a photobleached dynamical coordinate system 光漂白动态坐标系中马达驱动的微管扩散
Pub Date : 2024-08-20 DOI: arxiv-2408.11216
Soichi Hirokawa, Heun Jin Lee, Rachel A Banks, Ana I Duarte, Bibi Najma, Matt Thomson, Rob Phillips
Motor-driven cytoskeletal remodeling in cellular systems can often beaccompanied by a diffusive-like effect at local scales, but distinguishing thecontributions of the ordering process, such as active contraction of a network,from this active diffusion is difficult to achieve. Using light-dimerizablekinesin motors to spatially control the formation and contraction of amicrotubule network, we deliberately photobleach a grid pattern onto thefilament network serving as a transient and dynamic coordinate system toobserve the deformation and translation of the remaining fluorescent squares ofmicrotubules. We find that the network contracts at a rate set by motor speedbut is accompanied by a diffusive-like spread throughout the bulk of thecontracting network with effective diffusion constant two orders of magnitudelower than that for a freely-diffusing microtubule. We further find that onmicron scales, the diffusive timescale is only a factor of approximately 3slower than that of advection regardless of conditions, showing that the globalcontraction and long-time relaxation from this diffusive behavior are bothmotor-driven but exhibit local competition within the network bulk.
在细胞系统中,马达驱动的细胞骨架重塑往往伴随着局部尺度上的类似扩散效应,但是很难将有序化过程(如网络的主动收缩)与这种主动扩散区分开来。利用可光二聚化的驱动蛋白马达在空间上控制微管网络的形成和收缩,我们特意将网格图案光漂白到长丝网络上,作为一个瞬时动态坐标系来观察微管剩余荧光方格的变形和平移。我们发现,微管网络以马达速度设定的速率收缩,但在整个收缩网络中伴随着类似扩散的扩散,其有效扩散常数比自由扩散的微管低两个数量级。我们进一步发现,在微米尺度上,无论条件如何,扩散时间尺度仅比平流时间尺度慢约 3 倍,这表明这种扩散行为的全局收缩和长时间松弛都是由马达驱动的,但在网络主体内表现出局部竞争。
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引用次数: 0
期刊
arXiv - PHYS - Biological Physics
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