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In-silico model of the pregnant uterus as a network of oscillators under sparse adaptive control 作为稀疏自适应控制下振荡器网络的妊娠子宫内模拟模型
Pub Date : 2024-08-01 DOI: arxiv-2408.00956
Giuseppe Maria Ferro, Andrea Somazzi, Didier Sornette
To ensure optimal survival of the neonate, the biological timing ofparturition must be tightly controlled. Medical studies show that a variety ofendocrine systems play the role of a control system, establishing a dynamicbalance between the forces that cause uterine quiescence during pregnancy andthe forces that produce coordinated uterine contractility at parturition. Thesecontrol mechanism, and the factors that affect their performance, are stillpoorly understood. To help fill this gap, we propose a model of the pregnantuterus as a network of FitzHugh-Nagumo oscillators, with each cell symbolizingthe electrical activity of a myocyte. The model is augmented with sparseadaptive control mechanisms representing the regulating endocrine functions.The control system is characterized by the fraction of controlled sites, andstrength of control. We quantitatively find the conditions for which thecontrol system exhibit a balance between robustness (resilience againstperturbations) and flexibility (ability to switch function with minimal cost)crucial for optimal neonatal survival. Specifically, we show that Braxton-Hicksand Alvarez contractions, which are observed sporadic contractions of theuterine muscle, serve as a safety valve against over-controlling, strategicallysuppressed yet retained to optimize the control system's efficiency. Pretermbirth is suggested to be understood as a mis-identification of the controlboundaries. These insights contribute to advancing our understanding ofmaternal-fetal health.
为了确保新生儿的最佳存活率,必须严格控制分娩的生理时间。医学研究表明,各种内分泌系统扮演着控制系统的角色,在怀孕期间导致子宫静止的力量和分娩时产生协调子宫收缩的力量之间建立动态平衡。人们对这些控制机制以及影响其性能的因素仍然知之甚少。为了帮助填补这一空白,我们提出了一个妊娠子宫模型,它是一个由 FitzHugh-Nagumo 振荡器组成的网络,每个细胞象征一个肌细胞的电活动。该模型由代表内分泌调节功能的稀疏自适应控制机制来增强。控制系统的特征在于受控点的比例和控制强度。我们定量地找到了控制系统在稳健性(抵御干扰的能力)和灵活性(以最小代价切换功能的能力)之间取得平衡的条件,这对新生儿的最佳生存至关重要。具体来说,我们发现,子宫肌肉的布拉克斯顿-希克斯收缩和阿尔瓦雷斯收缩是一种可观察到的偶发性收缩,它们是防止过度控制的安全阀,在战略上受到抑制,但仍被保留下来,以优化控制系统的效率。早产被认为是对控制边界的错误识别。这些见解有助于加深我们对母体-胎儿健康的理解。
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引用次数: 0
Microscopic model for aging of biocondensates 生物凝结物老化的微观模型
Pub Date : 2024-07-31 DOI: arxiv-2407.21710
Hugo Le Roy, Paolo De Los Rios
Biomolecular condensates are membraneless compartments in the cell that areinvolved in a wide diversity of biological processes. These phase-separateddroplets usually exhibit a viscoelastic mechanical response. A behaviorrationalized by modeling the complex molecules that make up a condensate asstickers and spacers, which assemble into a network-like structure. The properfunctioning of biocondensates requires precise control over their composition,size, and mechanical response. For example, several neurodegenerative diseasesare associated with dysfunctional condensates that solidify over a long periodof time (days) until they become solid. A phenomenon usually described asaging. The emergence of such a long timescale of evolution from microscopicevents, as well as the associated microscopic reorganization leading to aging,remains mostly an open question. In this article, we explore the connectionbetween the mechanical properties of the condensates and their microscopicstructure. We propose a minimal model for the dynamic of stickers and spacers,and show that entropy minimization of spacers leads to an attractive forcebetween stickers. Our system displays a surprisingly slow relaxation towardequilibrium, reminiscent of glassy systems and consistent with theliquid-to-solid transition observed. To explain this behavior, we study theclustering dynamic of stickers and successfully explain the origin of glassyrelaxation.
生物分子凝聚体是细胞中的无膜区,参与了多种多样的生物过程。这些相分离的液滴通常表现出粘弹性机械响应。通过将组成凝结物的复杂分子建模为粘合剂和间隔物,这些粘合剂和间隔物会组装成网络状结构,从而使这种行为合理化。生物缩聚物的正常功能需要对其成分、大小和机械响应进行精确控制。例如,一些神经退行性疾病与功能失调的凝结物有关,这些凝结物会在很长一段时间(数天)内凝固,直至变成固体。这种现象通常被描述为衰老。从微观事件中产生如此长时间尺度的进化,以及导致衰老的相关微观重组,在很大程度上仍是一个未决问题。在本文中,我们探讨了凝聚态的机械特性与其微观结构之间的联系。我们提出了贴纸和间隔物动态的最小模型,并证明间隔物的熵最小化会导致贴纸之间产生吸引力。我们的系统显示出令人惊讶的向平衡的缓慢弛豫,这让人联想到玻璃态系统,并与所观察到的液态到固态的转变相一致。为了解释这种行为,我们研究了贴纸的聚类动态,并成功解释了玻璃态松弛的起源。
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引用次数: 0
SSPACE Astrobiology Payload-1 (SAP-1) SSPACE 天体生物学有效载荷-1(SAP-1)
Pub Date : 2024-07-30 DOI: arxiv-2407.21183
A Lokaveer, Thomas Anjana, Maliyekkal Yasir, S Yogahariharan, Akash Dewangan, Saurabh Kishor Mahajan, Sakshi Aravind Tembhurne, Gunja Subhash Gupta, Devashish Bhalla, Anantha Datta Dhruva, Aloke Kumar, Koushik Viswanathan, Vikram Khaire, Anand Narayanan, Priyadarshnam Hari
The SSPACE Astrobiology Payload (SAP) series, starting with the SAP-1 projectis designed to conduct in-situ microbiology experiments in low earth orbit.This payload series aims to understand the behaviour of microbial organisms inspace, particularly those critical for human health, and the correspondingeffects due to microgravity and solar/galactic radiation. SAP-1 focuses onstudying Bacillus clausii and Bacillus coagulans, bacteria beneficial tohumans. It aims to provide a space laboratory for astrobiology experimentsunder microgravity conditions. The hardware developed for these experiments isindigenous and tailored to meet the unique requirements of autonomousmicrobiology experiments by controlling pressure, temperature, and nutritionflow to bacteria. A rotating platform, which forms the core design, isinnovatively utilised to regulate the flow and mixing of nutrients with dormantbacteria. The technology demonstration models developed at SSPACE have yieldedpromising results, with ongoing efforts to refine, adapt for space conditions,and prepare for integration with nanosatellites or space modules. Theanticipated payload will be compact, approximately 1U in size (10cm x 10cm x10cm), consume less than 5W power, and offer flexibility for variousmicrobiological studies.
SSPACE 天体生物学有效载荷(SAP)系列,从 SAP-1 项目开始,旨在低地球轨道上进行原位微生物学实验。该有效载荷系列旨在了解空间微生物有机体的行为,特别是那些对人类健康至关重要的微生物有机体的行为,以及微重力和太阳/银河辐射造成的相应影响。SAP-1的重点是研究对人类有益的细菌Bacillus clausii和Bacillus coagulans。其目的是为微重力条件下的天体生物学实验提供一个空间实验室。为这些实验开发的硬件是本土的,通过控制压力、温度和细菌的营养流来满足自主微生物学实验的独特要求。构成核心设计的旋转平台被创新性地用于调节营养物质与休眠细菌的流动和混合。在 SSPACE 开发的技术示范模型已经取得了可喜的成果,目前正在努力进行改进,以适应太空条件,并为与纳米卫星或太空舱集成做好准备。预期的有效载荷将非常紧凑,大小约为 1U (10 厘米 x 10 厘米 x 10 厘米),功耗小于 5 瓦,并为各种微生物研究提供灵活性。
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引用次数: 0
Fragmentation and aggregation of cyanobacterial colonies 蓝藻菌落的破碎和聚集
Pub Date : 2024-07-30 DOI: arxiv-2407.21115
Yuri Z. Sinzato, Robert Uittenbogaard, Petra M. Visser, Jef Huisman, Maziyar Jalaal
Fluid flow has a major effect on the aggregation and fragmentation ofbacterial colonies. Yet, a generic framework to understand and predict howhydrodynamics affects colony size remains elusive. This study investigates howfluid flow affects the formation and maintenance of large colonial structuresin cyanobacteria. We performed experiments on laboratory cultures and lakesamples of the cyanobacterium Microcystis, while their colony size distributionwas measured simultaneously by direct microscopic imaging. We demonstrate thatEPS-embedded cells formed by cell division exhibit significant mechanicalresistance to shear forces. However, at elevated hydrodynamic stress levels(exceeding those typically generated by surface wind mixing) these coloniesexperience fragmentation through an erosion process. We also show that singlecells can aggregate into small colonies due to fluid flow. However, thestructural integrity of these flow-induced colonies is weaker than that ofcolonies formed by cell division. We provide a mathematical analysis to supportthe experiments and demonstrate that a population model with two categories ofcolonies describes the measured size distributions. Our results shed light onthe specific conditions wherein flow-induced fragmentation and aggregation ofcyanobacteria are decisive and indicate that colony formation under naturalconditions is mainly driven by cell division, although flow-induced aggregationcould play a role in dense bloom events. These findings can be used to improveprediction models and mitigation strategies for toxic cyanobacterial blooms andalso offer potential applications in other areas such as algal biotechnology ormedical settings where the dynamics of biological aggregates play a significantrole.
流体流动对细菌菌落的聚集和破碎有重大影响。然而,理解和预测流体动力学如何影响菌落大小的通用框架仍然遥不可及。本研究探讨了流体如何影响蓝藻大型菌落结构的形成和维持。我们对蓝藻微囊藻的实验室培养物和湖泊样本进行了实验,同时通过直接显微成像测量了它们的菌落大小分布。我们证明,由细胞分裂形成的 EPS 嵌入细胞对剪切力具有显著的机械阻力。然而,在流体动力应力水平升高时(超过通常由表面风混合产生的应力水平),这些菌落会通过侵蚀过程而破碎。我们还发现,单细胞会因流体流动而聚集成小菌落。然而,与细胞分裂形成的菌落相比,这些由流动引起的菌落的结构完整性较弱。我们提供了支持实验的数学分析,并证明包含两类菌落的种群模型可以描述测量到的大小分布。我们的研究结果揭示了在哪些特定条件下,水流诱导的蓝藻分裂和聚集起决定性作用,并表明自然条件下的菌落形成主要由细胞分裂驱动,尽管水流诱导的聚集可能在密集藻华事件中发挥作用。这些发现可用于改进有毒蓝藻藻华的预测模型和缓解策略,还可能应用于藻类生物技术或医疗等其他领域,因为生物聚集体的动力学在这些领域发挥着重要作用。
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引用次数: 0
Non-linear inhibitory responses enhance performance in collective decision-making 非线性抑制反应可提高集体决策的绩效
Pub Date : 2024-07-30 DOI: arxiv-2407.20927
David March-Pons, Romualdo Pastor-Satorras, M. Carmen Miguel
The precise modulation of activity through inhibitory signals ensures thatboth insect colonies and neural circuits operate efficiently and adaptively,highlighting the fundamental importance of inhibition in biological systems.Modulatory signals are produced in various contexts and are known for subtlyshifting the probability of receiver behaviors based on response thresholds.Here we propose a non-linear function to introduce inhibitory responsiveness incollective decision-making inspired by honeybee house-hunting. We show that,compared with usual linear functions, non-linear responses enhance finalconsensus and reduce deliberation time. This improvement comes at the cost ofreduced accuracy in identifying the best option. Nonetheless, for value-basedtasks, the benefits of faster consensus and enhanced decision-making mightoutweigh this drawback.
通过抑制信号对活动进行精确调制,确保了昆虫群落和神经回路的高效和适应性运行,这凸显了抑制在生物系统中的根本重要性。调制信号产生于各种环境中,并以根据反应阈值微妙地改变接收者行为的概率而闻名。在此,我们提出了一种非线性函数,在集体决策中引入抑制反应,其灵感来源于蜜蜂的捕房行为。我们的研究表明,与通常的线性函数相比,非线性反应增强了最终共识,减少了商议时间。这种改进的代价是降低了确定最佳方案的准确性。尽管如此,对于基于价值的任务来说,更快达成共识和增强决策的好处可能会超过这一缺点。
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引用次数: 0
Constrained motion of self-propelling eccentric disks linked by a spring 由弹簧连接的自推进偏心盘的受约束运动
Pub Date : 2024-07-30 DOI: arxiv-2407.20610
Tian-liang Xu, Chao-ran Qin, Bin Tang, Jin-cheng Gao, Jiankang Zhou, Kang Chen, Tian Hui Zhang, Wen-de Tian
It has been supposed that the interplay of elasticity and activity plays akey role in triggering the non-equilibrium behaviors in biological systems.However, the experimental model system is missing to investigate thespatiotemporally dynamical phenomena. Here, a model system of an active chain,where active eccentric-disks are linked by a spring, is designed to study theinterplay of activity, elasticity, and friction. Individual active chainexhibits longitudinal and transverse motion, however, it starts to self-rotatewhen pinning one end, and self-beats when clamping one end. Additionally, oureccentric-disk model can qualitatively reproduce such behaviors and explain theunusual self-rotation of the first disk around its geometric center. Further,the structure and dynamics of long chains were studied via simulations withoutsteric interactions. It was found that hairpin conformation emerges in freemotion, while in the constrained motions, the rotational and beatingfrequencies scale with the flexure number (the ratio of self-propelling forceto bending rigidity), ~4/3. Scaling analysis suggests that it results from thebalance between activity and energy dissipation. Our findings show thattopological constraints play a vital role in non-equilibrium synergy behavior.
人们认为,弹性和活动的相互作用在引发生物系统的非平衡行为中起着重要作用。然而,目前还缺少研究时空动态现象的实验模型系统。在此,我们设计了一个活动链模型系统来研究活动、弹性和摩擦的相互作用。单个主动链表现出纵向和横向运动,然而,当一端被夹住时,它开始自转,当一端被夹住时,它开始自跳。此外,我们的偏心圆盘模型可以定性地再现这些行为,并解释第一个圆盘围绕其几何中心的异常自转。此外,研究人员还通过无立体相互作用的模拟研究了长链的结构和动力学。结果发现,发夹构象出现在自由运动中,而在受约束运动中,旋转和跳动频率与弯曲数(自推动力与弯曲刚度之比)成比例关系,约为4/3。缩放分析表明,这是活动与能量耗散之间平衡的结果。我们的研究结果表明,表观约束在非平衡协同行为中起着至关重要的作用。
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引用次数: 0
Design of a System for Analyzing Cell Mechanics 设计细胞力学分析系统
Pub Date : 2024-07-30 DOI: arxiv-2407.21182
Hasan Berkay Abdioglu, Yagmur Isik, Merve Sevgi, Ufuk Gorkem Kirabali, Yunus Emre Mert, Gulnihal Guldogan, Selin Serdarli, Tarik Taha Gulen, Huseyin Uvet
Accurately measuring cell stiffness is challenging due to the invasiveness oftraditional methods like atomic force microscopy (AFM) and optical stretching.We introduce a non-invasive off-axis system using holographic imaging andacoustic stimulation. This system features an off-axis Mach-Zehnderinterferometer and bulk acoustic waves to capture cell mechanics. It employshigh-resolution components to create detailed interferograms and allowscontinuous imaging of cell deformation. Unlike conventional techniques, ourmethod provides high-throughput, label-free measurements while preserving cellintegrity. Polyacrylamide beads are tested for high precision, highlighting thepotential of the system in early cancer detection, disease monitoring, andmechanobiological research.
由于原子力显微镜(AFM)和光学拉伸等传统方法的侵入性,精确测量细胞硬度具有挑战性。该系统采用离轴马赫-泽恩德干涉仪和体声波来捕捉细胞力学。它采用高分辨率组件来创建详细的干涉图,并允许对细胞变形进行连续成像。与传统技术不同,我们的方法提供了高通量、无标记的测量,同时保持了细胞的完整性。聚丙烯酰胺珠经过高精度测试,凸显了该系统在早期癌症检测、疾病监测和机械生物学研究方面的潜力。
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引用次数: 0
Laser patterned diamond electrodes for adhesion and proliferation of human mesenchymal stem cells 用于人类间充质干细胞粘附和增殖的激光图案金刚石电极
Pub Date : 2024-07-28 DOI: arxiv-2407.19582
Hassan N. Al Hashem, Amanda N. Abraham, Deepak Sharma, Andre Chambers, Mehrnoosh Moghaddar, Chayla L. Reeves, Sanjay K. Srivastava, Amy Gelmi, Arman Ahnood
The ability to form diamond electrodes on insulating polycrystalline diamondsubstrates using single-step laser patterning, and the use of the electrodes asa substrate that supports the adhesion and proliferation of human mesenchymalstem cells (hMSCs) is demonstrated. Laser induced graphitisation results in aconductive amorphous carbon surface, rich in oxygen and nitrogen terminations.This results in an electrode with a high specific capacitance of 182 uF/cm2, awide water window of 3.25 V, and a low electrochemical impedance of 129Ohms/cm2 at 1 kHz. The electrodes surface exhibited a good level ofbiocompatibility with hMSCs, supporting cell adhesion and proliferation. Thecells cultured on the electrode displayed significant elongation and alignmentalong the direction of the laser patterned microgrooves. Because of itsfavourable electrochemical performance and biocompatibility, thelaser-patterned diamond electrodes create a potential for a versatile platformin stem cell therapeutics.
该研究展示了利用单步激光图案化技术在绝缘多晶金刚石基底上形成金刚石电极的能力,以及将这种电极用作支持人类间充质干细胞(hMSCs)粘附和增殖的基底的能力。激光诱导石墨化产生了富含氧和氮终端的导电无定形碳表面,从而使电极具有 182 uF/cm2 的高比电容、3.25 V 的宽水窗和 1 kHz 时 129Ohms/cm2 的低电化学阻抗。电极表面与 hMSCs 具有良好的生物相容性,支持细胞粘附和增殖。在电极上培养的细胞沿着激光图案微槽的方向有明显的伸长和排列。激光图案金刚石电极具有良好的电化学性能和生物相容性,有望成为干细胞治疗的多功能平台。
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引用次数: 0
Cell Sorting in an Active Nematic Vertex Model 活跃向列顶点模型中的细胞排序
Pub Date : 2024-07-28 DOI: arxiv-2407.19591
Jan Rozman, Julia M. Yeomans
We study a mixture of extensile and contractile cells using a vertex modelextended to include active nematic stresses. The two cell populations phaseseparate over time. While phase separation strengthens monotonically with anincreasing magnitude of contractile activity, the dependence on extensileactivity is non-monotonic, so that sufficiently high values reduce the extentof sorting. We interpret this by showing that extensile activity renders thesystem motile, enabling cells to undergo neighbour exchanges. Contractile cellsthat come into contact as a result are then more likely to stay connected dueto an effective attraction arising from contractile activity.
我们使用顶点模式研究了伸展细胞和收缩细胞的混合物,并将主动向列应力包括在内。随着时间的推移,两个细胞群会发生相分离。虽然相分离会随着收缩活性的增加而单调加强,但对伸展活性的依赖却是非单调的,因此足够高的值会降低分选的程度。我们对此的解释是,延伸活动使系统具有运动性,从而使细胞能够进行邻近交换。因此接触到的收缩细胞由于收缩活动产生的有效吸引力而更有可能保持连接。
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引用次数: 0
Criticality enhances the reinforcement of disordered networks by rigid inclusions 临界性增强了刚性夹杂物对无序网络的强化作用
Pub Date : 2024-07-28 DOI: arxiv-2407.19563
Jordan L. Shivers, Jingchen Feng, Fred C. MacKintosh
The mechanical properties of biological materials are spatiallyheterogeneous. Typical tissues are made up of a spanning fibrous extracellularmatrix in which various inclusions, such as living cells, are embedded. Whilethe influence of inclusions on the stiffness of common elastic materials suchas rubber has been studied for decades and can be understood in terms of thevolume fraction and shape of inclusions, the same is not true for disorderedfilamentous and fibrous networks. Recent work has shown that, in isolation,such networks exhibit unusual viscoelastic behavior indicative of an underlyingmechanical phase transition controlled by network connectivity and strain. Howthis behavior is modified when inclusions are present is unclear. Here, wepresent a theoretical and computational study of the influence of rigidinclusions on the mechanics of disordered elastic networks near theconnectivity-controlled central force rigidity transition. Combining scalingtheory and coarse-grained simulations, we predict and confirm an anomalouslystrong dependence of the composite stiffness on inclusion volume fraction,beyond that seen in ordinary composites. This stiffening exceeds thewell-established volume fraction-dependent stiffening expected in conventionalcomposites, e.g., as an elastic analogue of the classic volume fractiondependent increase in the viscosity of liquids first identified by Einstein. Weshow that this enhancement is a consequence of the interplay betweeninter-particle spacing and an emergent correlation length, leading to aneffective finite-size scaling imposed by the presence of inclusions. We outlinethe expected scaling of the shear modulus and strain fluctuations with theinclusion volume fraction and network connectivity, confirm these predictionsin simulations, and discuss potential experimental tests and implications forour predictions in real systems.
生物材料的机械特性在空间上是异质的。典型的组织由横跨的纤维状细胞外基质构成,其中嵌入了各种内含物,如活细胞。几十年来,人们一直在研究内含物对橡胶等普通弹性材料刚度的影响,并且可以从内含物的体积分数和形状来理解这种影响,但对于无序的丝状和纤维状网络来说,情况却并非如此。最近的研究表明,在孤立的情况下,此类网络表现出不寻常的粘弹性行为,表明其背后的机械相变受网络连通性和应变的控制。目前还不清楚在存在夹杂物的情况下,这种行为会发生怎样的变化。在此,我们将对刚性夹杂物在连通性控制的中心力刚性转变附近对无序弹性网络力学的影响进行理论和计算研究。结合缩放理论和粗粒度模拟,我们预测并证实了复合材料刚度对夹杂物体积分数的异常强依赖性,这种依赖性超出了普通复合材料。这种刚度的增强超出了传统复合材料中已被证实的与体积分数相关的刚度增强,例如,爱因斯坦首次发现的液体粘度增加与体积分数相关的典型弹性类似。我们认为,这种增强是粒子间距和新出现的相关长度之间相互作用的结果,从而导致因夹杂物的存在而产生的有效有限尺寸缩放。我们概述了剪切模量和应变波动与夹杂物体积分数和网络连通性的预期比例关系,在模拟中证实了这些预测,并讨论了可能的实验测试以及我们的预测在实际系统中的影响。
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引用次数: 0
期刊
arXiv - PHYS - Biological Physics
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