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An integrative biology approach to understanding keratinocyte collective migration as stimulated by bioglass. 用综合生物学方法理解生物玻璃刺激的角质细胞集体迁移。
IF 2.5 4区 生物学 Q1 Medicine Pub Date : 2024-01-23 DOI: 10.1093/intbio/zyae008
Joseph Siegfreid, Ali Crampton, Saghi Saghazadeh, Randilynn Christensen, Jacob Notbohm, Jason Bjork, Bryan Baker

A critical phase of wound healing is the coordinated movement of keratinocytes. To this end, bioglasses show promise in speeding healing in hard tissues and skin wounds. Studies suggest that bioglass materials may promote wound healing by inducing positive cell responses in proliferation, growth factor production, expression of angiogenic factors, and migration. Precise details of how bioglass may stimulate migration are unclear, however, because the common assays for studying migration in wound healing focus on simplified outputs like rate of migration or total change in wound area. These outputs are limited in that they represent the average behavior of the collective, with no connection between the motion of the individual cells and the collective wound healing response. There is a need to apply more refined tools that identify how the motion of the individual cells changes in response to perturbations, such as by bioglass, and in turn affects motion of the cell collective. Here, we apply an integrative biology strategy that combines an in vitro wound healing assay using primary neonatal human keratinocytes with time lapse microscopy and quantitative image analysis. The resulting data set provides the cell velocity field, from which we define key metrics that describe cooperative migration phenotypes. Treatment with growth factors led to faster single-cell speeds compared to control, but the migration was not cooperative, with cells breaking away from their neighbors and migrating as individuals. Treatment with calcium or bioglass led to migration phenotypes that were highly collective, with greater coordination in space compared to control. We discuss the link between bioglass treatment and observed increases in free calcium ions that are hypothesized to promote these distinct coordinated behaviors in primary keratinocytes. These findings have been enabled by the unique descriptors developed through applying image analysis to interpret biological response in migration models. Insight Box/Paragraph Statement: Bioglasses are important materials for tissue engineering and have more recently shown promise in skin and wound healing by mechanisms tied to their unique ionic properties. The precise details, however, of how cell migration may be affected by bioglass are left unclear by traditional cell assay methods. The following describes the integration of migration assays of keratinocytes, cells critical for skin and wound healing, with the tools of time lapse microscopy and image analysis to generate a quantitative description of coordinated, tissue-like migration behavior, stimulated by bioglass, that would not have been accessible without the combination of these analytical tools.

伤口愈合的一个关键阶段是角质细胞的协调运动。为此,生物玻璃有望加速硬组织和皮肤伤口的愈合。研究表明,生物玻璃材料可通过诱导细胞在增殖、产生生长因子、表达血管生成因子和迁移方面的积极反应来促进伤口愈合。然而,生物玻璃如何刺激迁移的具体细节尚不清楚,因为研究伤口愈合中迁移的常用方法侧重于简化的输出,如迁移率或伤口面积的总变化。这些结果是有限的,因为它们代表的是集体的平均行为,单个细胞的运动与集体的伤口愈合反应之间没有联系。我们需要应用更精细的工具,以确定单个细胞的运动如何对生物玻璃等扰动做出反应,进而影响细胞集体的运动。在这里,我们采用了一种综合生物学策略,将使用原代新生人类角质细胞进行的体外伤口愈合试验与延时显微镜和定量图像分析相结合。由此产生的数据集提供了细胞速度场,我们据此定义了描述合作迁移表型的关键指标。与对照组相比,使用生长因子处理可使单细胞速度加快,但迁移并不合作,细胞会脱离邻近细胞,作为个体迁移。与对照组相比,用钙或生物玻璃处理会导致高度集体的迁移表型,在空间上有更大的协调性。我们讨论了生物玻璃处理与观察到的游离钙离子增加之间的联系,假设游离钙离子的增加促进了原代角质形成细胞中这些不同的协调行为。这些发现得益于通过应用图像分析来解释迁移模型中的生物反应而开发的独特描述符。洞察框/段落陈述:生物玻璃是组织工程学的重要材料,最近在皮肤和伤口愈合方面显示出与其独特离子特性相关的机制。然而,传统的细胞检测方法并不清楚生物玻璃如何影响细胞迁移的具体细节。下文介绍了如何将角质形成细胞(对皮肤和伤口愈合至关重要的细胞)的迁移测定与延时显微镜和图像分析工具相结合,从而对生物玻璃刺激下的协调组织样迁移行为进行定量描述。
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引用次数: 0
Mechanical factors influence β-catenin localization and barrier properties. 机械因素影响β-catenin的定位和屏障特性。
IF 1.5 4区 生物学 Q4 CELL BIOLOGY Pub Date : 2024-01-23 DOI: 10.1093/intbio/zyae013
Xi Wu, Nikola Cesarovic, Volkmar Falk, Edoardo Mazza, Costanza Giampietro

Mechanical forces are of major importance in regulating vascular homeostasis by influencing endothelial cell behavior and functions. Adherens junctions are critical sites for mechanotransduction in endothelial cells. β-catenin, a component of adherens junctions and the canonical Wnt signaling pathway, plays a role in mechanoactivation. Evidence suggests that β-catenin is involved in flow sensing and responds to tensional forces, impacting junction dynamics. The mechanoregulation of β-catenin signaling is context-dependent, influenced by the type and duration of mechanical loads. In endothelial cells, β-catenin's nuclear translocation and signaling are influenced by shear stress and strain, affecting endothelial permeability. The study investigates how shear stress, strain, and surface topography impact adherens junction dynamics, regulate β-catenin localization, and influence endothelial barrier properties. Insight box Mechanical loads are potent regulators of endothelial functions through not completely elucidated mechanisms. Surface topography, wall shear stress and cyclic wall deformation contribute overlapping mechanical stimuli to which endothelial monolayer respond to adapt and maintain barrier functions. The use of custom developed flow chamber and bioreactor allows quantifying the response of mature human endothelial to well-defined wall shear stress and gradients of strain. Here, the mechanoregulation of β-catenin by substrate topography, wall shear stress, and cyclic stretch is analyzed and linked to the monolayer control of endothelial permeability.

机械力通过影响内皮细胞的行为和功能,在调节血管稳态方面发挥着重要作用。粘连接头是内皮细胞机械传导的关键位置。β-catenin是粘连接头和典型Wnt信号通路的组成部分,在机械激活中发挥作用。有证据表明,β-catenin 参与流动感应并对张力做出反应,从而影响连接动态。β-catenin信号传导的机械调节依赖于环境,受机械负荷类型和持续时间的影响。在内皮细胞中,β-catenin 的核转位和信号传导受剪切应力和应变的影响,从而影响内皮细胞的通透性。该研究探讨了剪切应力、应变和表面形貌如何影响粘连接头动态、调控β-catenin定位以及影响内皮屏障特性。洞察框 机械负荷通过尚未完全阐明的机制对内皮功能起着强有力的调节作用。表面形貌、管壁剪切应力和周期性管壁变形会产生重叠的机械刺激,内皮单层会对这些刺激做出反应,以适应和维持屏障功能。使用定制开发的流室和生物反应器可以量化成熟的人类内皮对明确定义的壁剪应力和应变梯度的反应。本文分析了β-catenin受基底地形、壁剪切应力和循环拉伸的机械调节,并将其与内皮通透性的单层控制联系起来。
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引用次数: 0
A multilayer microfluidic system for studies of the dynamic responses of cellular proteins to oxygen switches at the single-cell level. 用于在单细胞水平研究细胞蛋白质对氧气开关的动态响应的多层微流体系统。
IF 2.5 4区 生物学 Q1 Medicine Pub Date : 2024-01-23 DOI: 10.1093/intbio/zyae011
Wei Fu, Shujing Wang, Qi Ouyang, Chunxiong Luo

Oxygen levels vary in the environment. Oxygen availability has a major effect on almost all organisms, and oxygen is far more than a substrate for energy production. However, less is known about related biological processes under hypoxic conditions and about the adaptations to changing oxygen concentrations. The yeast Saccharomyces cerevisiae can adapt its metabolism for growth under different oxygen concentrations and can grow even under anaerobic conditions. Therefore, we developed a microfluidic device that can generate serial, accurately controlled oxygen concentrations for single-cell studies of multiple yeast strains. This device can construct a broad range of oxygen concentrations, [O2] through on-chip gas-mixing channels from two gases fed to the inlets. Gas diffusion through thin polydimethylsiloxane (PDMS) can lead to the equilibration of [O2] in the medium in the cell culture layer under gas cover regions within 2 min. Here, we established six different and stable [O2] varying between ~0.1 and 20.9% in the corresponding layers of the device designed for multiple parallel single-cell culture of four different yeast strains. Using this device, the dynamic responses of different yeast transcription factors and metabolism-related proteins were studied when the [O2] decreased from 20.9% to serial hypoxic concentrations. We showed that different hypoxic conditions induced varying degrees of transcription factor responses and changes in respiratory metabolism levels. This device can also be used in studies of the aging and physiology of yeast under different oxygen conditions and can provide new insights into the relationship between oxygen and organisms. Integration, innovation and insight: Most living cells are sensitive to the oxygen concentration because they depend on oxygen for survival and proper cellular functions. Here, a composite microfluidic device was designed for yeast single-cell studies at a series of accurately controlled oxygen concentrations. Using this device, we studied the dynamic responses of various transcription factors and proteins to changes in the oxygen concentration. This study is the first to examine protein dynamics and temporal behaviors under different hypoxic conditions at the single yeast cell level, which may provide insights into the processes involved in yeast and even mammalian cells. This device also provides a base model that can be extended to oxygen-related biology and can acquire more information about the complex networks of organisms.

环境中的氧气含量各不相同。氧气的可用性对几乎所有生物都有重大影响,氧气的作用远不止是产生能量的底物。然而,人们对缺氧条件下的相关生物过程以及对氧气浓度变化的适应性知之甚少。酵母菌能适应不同氧浓度下的新陈代谢,甚至能在厌氧条件下生长。因此,我们开发了一种微流控装置,可以产生序列化、精确控制的氧气浓度,用于多个酵母菌株的单细胞研究。该装置可通过片上气体混合通道,从两种气体输入入口处构建出范围广泛的氧气浓度[O2]。气体通过薄薄的聚二甲基硅氧烷(PDMS)扩散,可在 2 分钟内使气体覆盖区域内细胞培养层培养基中的[O2]达到平衡。在这里,我们在为四种不同酵母菌株的多重平行单细胞培养而设计的装置的相应层中建立了六种不同且稳定的[O2],其变化范围在 ~0.1% 到 20.9% 之间。利用该装置,研究了当[O2]从20.9%下降到系列缺氧浓度时,不同酵母转录因子和代谢相关蛋白的动态反应。我们发现,不同的缺氧条件会诱导不同程度的转录因子反应和呼吸代谢水平的变化。该装置还可用于研究不同氧气条件下酵母菌的衰老和生理学,并能为氧气与生物体之间的关系提供新的见解。整合、创新和洞察力:大多数活细胞对氧气浓度都很敏感,因为它们的生存和正常细胞功能都依赖于氧气。在这里,我们设计了一种复合微流体装置,用于在一系列精确控制的氧气浓度下进行酵母单细胞研究。利用该装置,我们研究了各种转录因子和蛋白质对氧气浓度变化的动态响应。这项研究首次在单个酵母细胞水平上研究了不同缺氧条件下蛋白质的动态和时间行为,为了解酵母甚至哺乳动物细胞的相关过程提供了启示。该装置还提供了一个基础模型,可扩展到与氧气相关的生物学领域,并能获取更多有关生物体复杂网络的信息。
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引用次数: 0
A systems framework for investigating the roles of multiple transporters and their impact on drug resistance. 研究多种转运体的作用及其对耐药性影响的系统框架。
IF 2.5 4区 生物学 Q1 Medicine Pub Date : 2024-01-23 DOI: 10.1093/intbio/zyae007
Manfredi di San Germano, J Krishnan

Efflux transporters are a fundamental component of both prokaryotic and eukaryotic cells, play a crucial role in maintaining cellular homeostasis, and represent a key bridge between single cell and population levels. From a biomedical perspective, they play a crucial role in drug resistance (and especially multi-drug resistance, MDR) in a range of systems spanning bacteria and human cancer cells. Typically, multiple efflux transporters are present in these cells, and the efflux transporters transport a range of substrates (with partially overlapping substrates between transporters). Furthermore, in the context of drug resistance, the levels of transporters may be elevated either due to extra or intracellular factors (feedforward regulation) or due to the drug itself (feedback regulation). As a consequence, there is a real need for a transparent systems-level understanding of the collective functioning of a set of transporters and their response to one or more drugs. We develop a systems framework for this purpose and examine the functioning of sets of transporters, their interplay with one or more drugs and their regulation (both feedforward and feedback). Using computational and analytical work, we obtain transparent insights into the systems level functioning of a set of transporters arising from the interplay between the multiplicity of drugs and transporters, different drug-transporter interaction parameters, sequestration and feedback and feedforward regulation. These insights transparently arising from the most basic consideration of a multiplicity of transporters have broad relevance in natural biology, biomedical engineering and synthetic biology. Insight, Innovation, Integration: Innovation: creating a structured systems framework for evaluating the impact of multiple transporters on drug efflux and drug resistance. Systematic analysis allows us to evaluate the effect of multiple transporters on one/more drugs, and dissect associated resistance mechanisms. Integration allows for elucidation of key cause-and-effect relationships and a transparent systems-level understanding of the collective functioning of transporters and their impact on resistance, revealing the interplay of key underlying factors. Systems-level insights include the essentially different behaviour of transporters as part of a group; unintuitive effects of influx; effects of elevated transporter-levels by feedforward and drug-induced mechanisms. Relevance: a systems understanding of efflux, their role in MDR, providing a framework/platform for use in designing treatment, and in synthetic biology design.

外排转运体是原核细胞和真核细胞的基本组成部分,在维持细胞平衡方面发挥着关键作用,是连接单细胞和群体水平的重要桥梁。从生物医学的角度来看,它们在细菌和人类癌细胞等一系列系统的耐药性(尤其是多重耐药性,MDR)中发挥着至关重要的作用。这些细胞中通常存在多个外排转运体,外排转运体转运一系列底物(转运体之间有部分底物重叠)。此外,在耐药性的情况下,转运体的水平可能会因细胞外或细胞内因素(前馈调节)或药物本身(反馈调节)而升高。因此,我们亟需从系统层面了解一组转运体的整体功能及其对一种或多种药物的反应。为此,我们开发了一个系统框架,研究了一组转运体的功能、它们与一种或多种药物的相互作用以及它们的调节(前馈和反馈)。通过计算和分析工作,我们从药物和转运体的多样性、不同药物与转运体的相互作用参数、螯合以及反馈和前馈调节之间的相互作用中,获得了对一组转运体的系统级功能的透彻见解。从对多种转运体的最基本考虑中得出的这些深刻见解,对自然生物学、生物医学工程和合成生物学具有广泛的意义。洞察、创新、整合:创新:创建结构化系统框架,评估多种转运体对药物外流和耐药性的影响。通过系统分析,我们可以评估多种转运体对一种/多种药物的影响,并剖析相关的耐药性机制。通过整合可以阐明关键的因果关系,并从系统层面透彻了解转运体的整体功能及其对耐药性的影响,揭示关键潜在因素的相互作用。系统层面的见解包括:作为群体一部分的转运体本质上的不同行为;流入的非直观影响;前馈和药物诱导机制对转运体水平升高的影响。相关性:对药物外流及其在 MDR 中作用的系统认识,为设计治疗方法和合成生物学设计提供框架/平台。
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引用次数: 0
Hub genes, key miRNAs and interaction analyses in type 2 diabetes mellitus: an integrative in silico approach. 2 型糖尿病中的枢纽基因、关键 miRNA 和相互作用分析:一种综合的硅学方法。
IF 2.5 4区 生物学 Q1 Medicine Pub Date : 2024-01-23 DOI: 10.1093/intbio/zyae002
Zeinab Nematollahi, Shiva Karimian, Ali Taghavirashidizadeh, Mohammad Darvishi, SeyedAbbas Pakmehr, Amin Erfan, Mohammad Javad Teimoury, Neda Mansouri, Iraj Alipourfard

Diabetes is a rising global metabolic disorder and leads to long-term consequences. As a multifactorial disease, the gene-associated mechanisms are important to know. This study applied a bioinformatics approach to explore the molecular underpinning of type 2 diabetes mellitus through differential gene expression analysis. We used microarray datasets GSE16415 and GSE29226 to identify differentially expressed genes between type 2 diabetes and normal samples using R software. Following that, using the STRING database, the protein-protein interaction network was constructed and further analyzed by Cytoscape software. The EnrichR database was used for Gene Ontology and pathway enrichment analysis to explore key pathways and functional annotations of hub genes. We also used miRTarBase and TargetScan databases to predict miRNAs targeting hub genes. We identified 21 hub genes in type 2 diabetes, some showing more significant changes in the PPI network. Our results revealed that GLUL, SLC32A1, PC, MAPK10, MAPT, and POSTN genes are more important in the PPI network and can be experimentally investigated as therapeutic targets. Hsa-miR-492 and hsa-miR-16-5p are suggested for diagnosis and prognosis by targeting GLUL, SLC32A1, PC, MAPK10, and MAPT genes involved in the insulin signaling pathway. Insight: Type 2 diabetes, as a rising global and multifactorial disorder, is important to know the gene-associated mechanisms. In an integrative bioinformatics analysis, we integrated different finding datasets to put together and find valuable diagnostic and prognostic hub genes and miRNAs. In contrast, genes, RNAs, and enzymes interact systematically in pathways. Using multiple databases and software, we identified differential expression between hub genes of diabetes and normal samples. We explored different protein-protein interaction networks, gene ontology, key pathway analysis, and predicted miRNAs that target hub genes. This study reported 21 significant hub genes and some miRNAs in the insulin signaling pathway for innovative and potential diagnostic and therapeutic purposes.

糖尿病是一种日益严重的全球性代谢性疾病,会导致长期后果。作为一种多因素疾病,了解与基因相关的机制非常重要。本研究采用生物信息学方法,通过差异基因表达分析探索 2 型糖尿病的分子基础。我们使用微阵列数据集 GSE16415 和 GSE29226,利用 R 软件识别 2 型糖尿病样本与正常样本之间的差异表达基因。随后,我们利用 STRING 数据库构建了蛋白质-蛋白质相互作用网络,并通过 Cytoscape 软件进行了进一步分析。EnrichR 数据库用于基因本体论和通路富集分析,以探索关键通路和枢纽基因的功能注释。我们还利用 miRTarBase 和 TargetScan 数据库预测了靶向枢纽基因的 miRNA。我们在 2 型糖尿病中发现了 21 个枢纽基因,其中一些在 PPI 网络中显示出更显著的变化。我们的结果显示,GLUL、SLC32A1、PC、MAPK10、MAPT 和 POSTN 基因在 PPI 网络中更为重要,可作为治疗靶点进行实验研究。通过靶向参与胰岛素信号通路的 GLUL、SLC32A1、PC、MAPK10 和 MAPT 基因,建议将 Hsa-miR-492 和 hsa-miR-16-5p 用于诊断和预后。启示2 型糖尿病是一种不断上升的全球性多因素疾病,了解与之相关的基因机制非常重要。在一项综合生物信息学分析中,我们整合了不同的发现数据集,以汇总并找到有价值的诊断和预后枢纽基因和 miRNA。相反,基因、RNA 和酶在通路中系统地相互作用。利用多个数据库和软件,我们确定了糖尿病和正常样本中枢基因的差异表达。我们探索了不同的蛋白-蛋白相互作用网络、基因本体、关键通路分析,并预测了靶向枢纽基因的 miRNA。本研究报告了胰岛素信号通路中的 21 个重要枢纽基因和一些 miRNA,具有创新性和潜在的诊断和治疗用途。
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引用次数: 0
The cellular zeta potential: cell electrophysiology beyond the membrane. 细胞泽塔电位:超越膜的细胞电生理学。
IF 2.5 4区 生物学 Q1 Medicine Pub Date : 2024-01-23 DOI: 10.1093/intbio/zyae003
Michael Pycraft Hughes

The standard model of the cell membrane potential Vm describes it as arising from diffusion currents across a membrane with a constant electric field, with zero electric field outside the cell membrane. However, the influence of Vm has been shown to extend into the extracellular space where it alters the cell's ζ-potential, the electrical potential measured a few nm from the cell surface which defines how the cell interacts with charged entities in its environment, including ions, molecules, and other cells. The paradigm arising from surface science is that the ζ-potential arises only from fixed membrane surface charge, and has consequently received little interest. However, if the ζ-potential can mechanistically and dynamically change by alteration of Vm, it allows the cell to dynamically alter cell-cell and cell-molecule interactions and may explain previously unexplained electrophysiological behaviours. Whilst the two potentials Vm and ζ are rarely reported together, they are occasionally described in different studies for the same cell type. By considering published data on these parameters across multiple cell types, as well as incidences of unexplained but seemingly functional Vm changes correlating with changes in cell behaviour, evidence is presented that this may play a functional role in the physiology of red blood cells, macrophages, platelets, sperm, ova, bacteria and cancer. Understanding how these properties will improve understanding of the role of electrical potentials and charges in the regulation of cell function and in the way in which cells interact with their environment. Insight  The zeta (ζ) potential is the electrical potential a few nm beyond the surface of any suspensoid in water. Whilst typically assumed to arise only from fixed charges on the cell surface, recent and historical evidence shows a strong link to the cell's membrane potential Vm, which the cell can alter mechanistically through the use of ion channels. Whilst these two potentials have rarely been studied simultaneously, this review collates data across multiple studies reporting Vm, ζ-potential, electrical properties of changes in cell behaviour. Collectively, this points to Vm-mediated ζ-potential playing a significant role in the physiology and activity of blood cells, immune response, developmental biology and egg fertilization, and cancer among others.

细胞膜电位 Vm 的标准模型将其描述为产生于恒定电场下的跨膜扩散电流,细胞膜外的电场为零。然而,Vm 的影响已被证明可延伸至细胞外空间,它改变了细胞的 ζ 电位,即在距离细胞表面几纳米处测得的电位,它决定了细胞如何与其环境中的带电实体(包括离子、分子和其他细胞)相互作用。表面科学的范式认为,ζ电位仅由固定的膜表面电荷产生,因此很少引起人们的兴趣。然而,如果ζ电位能通过改变 Vm 发生机械和动态的变化,就能使细胞动态地改变细胞-细胞和细胞-分子之间的相互作用,并能解释以前无法解释的电生理行为。虽然 Vm 和 ζ 这两个电位很少被同时报道,但它们偶尔会在针对同一细胞类型的不同研究中被描述。通过考虑已发表的有关多种细胞类型的这些参数的数据,以及无法解释但似乎具有功能性的 Vm 变化与细胞行为变化相关的事件,有证据表明这可能在红细胞、巨噬细胞、血小板、精子、卵子、细菌和癌症的生理学中发挥功能性作用。了解这些特性将有助于更好地理解电位和电荷在调节细胞功能以及细胞与环境相互作用方面的作用。洞察力 zeta (ζ)电位是指水中任何悬浮体表面外几纳米处的电位。虽然人们通常认为zeta电位仅来自细胞表面的固定电荷,但最近和历史上的证据表明,zeta电位与细胞的膜电位Vm有密切联系,细胞可通过使用离子通道从机制上改变膜电位Vm。虽然这两种电位很少被同时研究,但本综述整理了报告 Vm、ζ电位、细胞行为变化的电特性的多项研究数据。总体而言,这表明 Vm 介导的ζ电位在血细胞的生理和活动、免疫反应、发育生物学和卵子受精以及癌症等方面发挥着重要作用。
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引用次数: 0
Asymmetric response emerges between creation and disintegration of force-bearing subcellular structures as revealed by percolation analysis. 渗流分析显示,受力亚细胞结构的形成和解体之间出现了不对称反应。
IF 2.5 4区 生物学 Q1 Medicine Pub Date : 2024-01-23 DOI: 10.1093/intbio/zyae012
Yuika Ueda, Daiki Matsunaga, Shinji Deguchi

Cells dynamically remodel their internal structures by modulating the arrangement of actin filaments (AFs). In this process, individual AFs exhibit stochastic behavior without knowing the macroscopic higher-order structures they are meant to create or disintegrate, but the mechanism allowing for such stochastic process-driven remodeling of subcellular structures remains incompletely understood. Here we employ percolation theory to explore how AFs interacting only with neighboring ones without recognizing the overall configuration can nonetheless create a substantial structure referred to as stress fibers (SFs) at particular locations. We determined the interaction probabilities of AFs undergoing cellular tensional homeostasis, a fundamental property maintaining intracellular tension. We showed that the duration required for the creation of SFs is shortened by the increased amount of preexisting actin meshwork, while the disintegration occurs independently of the presence of actin meshwork, suggesting that the coexistence of tension-bearing and non-bearing elements allows cells to promptly transition to new states in accordance with transient environmental changes. The origin of this asymmetry between creation and disintegration, consistently observed in actual cells, is elucidated through a minimal model analysis by examining the intrinsic nature of mechano-signal transmission. Specifically, unlike the symmetric case involving biochemical communication, physical communication to sense environmental changes is facilitated via AFs under tension, while other free AFs dissociated from tension-bearing structures exhibit stochastic behavior. Thus, both the numerical and minimal models demonstrate the essence of intracellular percolation, in which macroscopic asymmetry observed at the cellular level emerges not from microscopic asymmetry in the interaction probabilities of individual molecules, but rather only as a consequence of the manner of the mechano-signal transmission. These results provide novel insights into the role of the mutual interplay between distinct subcellular structures with and without tension-bearing capability. Insight: Cells continuously remodel their internal elements or structural proteins in response to environmental changes. Despite the stochastic behavior of individual structural proteins, which lack awareness of the larger subcellular structures they are meant to create or disintegrate, this self-assembly process somehow occurs to enable adaptation to the environment. Here we demonstrated through percolation simulations and minimal model analyses that there is an asymmetry in the response between the creation and disintegration of subcellular structures, which can aid environmental adaptation. This asymmetry inherently arises from the nature of mechano-signal transmission through structural proteins, namely tension-mediated information exchange within cells, despite the stochastic behavior of individual proteins lackin

细胞通过调节肌动蛋白丝(AF)的排列动态重塑其内部结构。在这一过程中,单个肌动蛋白丝表现出随机行为,而不知道它们要创建或瓦解的宏观高阶结构,但这种随机过程驱动亚细胞结构重塑的机制仍未完全清楚。在这里,我们运用渗滤理论来探讨仅与相邻AF相互作用而不识别整体构型的AF如何能在特定位置创建被称为应力纤维(SF)的实质性结构。我们确定了发生细胞张力平衡的 AFs 的相互作用概率,这是维持细胞内张力的基本特性。我们的研究表明,应力纤维的形成所需的时间会因预先存在的肌动蛋白网的增加而缩短,而应力纤维的解体则与肌动蛋白网的存在无关,这表明张力承载元素和非承载元素的共存使细胞能够根据瞬时的环境变化迅速过渡到新的状态。通过对机械信号传输的内在本质进行研究,我们通过最小模型分析阐明了在实际细胞中持续观察到的这种创造与解体之间不对称现象的起源。具体来说,与涉及生化通讯的对称情况不同,感知环境变化的物理通讯是通过受张力作用的 AF 促进的,而与受张力作用结构分离的其他自由 AF 则表现出随机行为。因此,数值模型和最小模型都证明了细胞内渗滤的本质,在细胞水平上观察到的宏观不对称性并非来自单个分子相互作用概率的微观不对称性,而仅仅是机械信号传输方式的结果。这些结果为了解具有和不具有张力承受能力的不同亚细胞结构之间相互影响的作用提供了新的视角。洞察力:细胞不断重塑其内部元素或结构蛋白,以应对环境变化。尽管单个结构蛋白的行为是随机的,它们对自己要创建或分解的更大的亚细胞结构缺乏认识,但这种自组装过程还是以某种方式发生了,从而实现了对环境的适应。在这里,我们通过渗流模拟和最小模型分析证明,亚细胞结构的创建和解体之间存在不对称反应,这有助于环境适应。尽管单个蛋白质的随机行为本身并不具有非对称特征,但这种非对称性本质上源于通过结构蛋白传递机械信号的性质,即细胞内张力介导的信息交流。
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引用次数: 0
Correction to: The cellular zeta potential: cell electrophysiology beyond the membrane. Correction to:细胞泽塔电位:超越膜的细胞电生理学。
IF 2.5 4区 生物学 Q1 Medicine Pub Date : 2024-01-23 DOI: 10.1093/intbio/zyae006
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引用次数: 0
Integrated analysis revealing novel associations between dietary patterns and the immune system in older adults. 综合分析揭示了老年人饮食模式与免疫系统之间的新关联。
IF 2.5 4区 生物学 Q1 Medicine Pub Date : 2024-01-23 DOI: 10.1093/intbio/zyae010
Jessica Conway, Animesh Acharjee, Niharika A Duggal

With the expanding ageing population, there is a growing interest in the maintenance of immune health to support healthy ageing. Enthusiasm exists for unravelling the impact of diet on the immune system and its therapeutic potential. However, a key challenge is the lack of studies investigating the effect of dietary patterns and nutrients on immune responses. Thus, we have used an integrative analysis approach to improve our understanding of diet-immune system interactions in older adults. To do so, dietary data were collected in parallel with performing immunophenotyping and functional assays from healthy older (n = 40) participants. Food Frequency Questionnaire (FFQ) was utilised to derive food group intake and multi-colour flow cytometry was performed for immune phenotypic and functional analysis. Spearman correlation revealed the strength of association between all combinations of dietary components, micronutrients, and hallmarks of immunesenescence. In this study, we propose for the first time that higher adherence to the Mediterranean diet is associated with a positive immune-ageing trajectory (Lower IMM-AGE score) in older adults due to the immune protective effects of high dietary fibre and PUFA intake in combating accumulation or pro-inflammatory senescent T cells. Furthermore, a diet rich in Vit A, Vit B6 and Vit B12 is associated with fewer features of immunesenescence [such as accumulation of terminally differentiated memory CD8 T cells] in older adults. Based on our findings we propose a future nutrition-based intervention study evaluating the efficacy of adherence to the MED diet alongside a multi-nutrient supplementation on immune ageing in older adults to set reliable dietary recommendations with policymakers that can be given to geriatricians and older adults. Insight box: There is a growing interest in the maintenance of immune health to boost healthy ageing. However, a key challenge is the lack of studies investigating the effect of dietary patterns and nutrients on immune responses. Thus, to do so we collected dietary data in parallel with performing immunophenotyping and functional assays on healthy older (n = 40) participants, followed by an integrative analysis approach to improve our understanding of diet-immune system interactions in older adults. We strongly believe that these new findings are appropriate for IB and will be of considerable interest to its broad audience.

随着老龄化人口的不断增加,人们对保持免疫健康以支持健康老龄化的兴趣与日俱增。人们热衷于研究饮食对免疫系统的影响及其治疗潜力。然而,一个关键的挑战是缺乏调查膳食模式和营养素对免疫反应影响的研究。因此,我们采用了一种综合分析方法来加深我们对老年人饮食与免疫系统相互作用的了解。为此,我们在收集饮食数据的同时,还对健康的老年人(40 人)进行了免疫分型和功能测定。利用食物频率问卷调查(FFQ)得出食物组摄入量,并采用多色流式细胞术进行免疫表型和功能分析。斯皮尔曼相关性显示了所有膳食成分、微量营养素组合与免疫衰老特征之间的关联强度。在这项研究中,我们首次提出,较高的地中海饮食坚持率与老年人的免疫衰老轨迹(较低的 IMM-AGE 分数)呈正相关,这是因为高膳食纤维和多酚类脂肪酸摄入量具有免疫保护作用,可防止促炎性衰老 T 细胞的积累。此外,富含维生素 A、维生素 B6 和维生素 B12 的饮食与老年人较少的免疫衰老特征(如终末分化记忆 CD8 T 细胞的积累)有关。根据我们的研究结果,我们建议未来开展一项基于营养的干预研究,评估在坚持 MED 饮食的同时补充多种营养素对老年人免疫衰老的影响,以便与决策者一起制定可靠的饮食建议,提供给老年病学家和老年人。透视框:人们对保持免疫健康以促进健康老龄化的兴趣与日俱增。然而,一个主要的挑战是缺乏调查膳食模式和营养素对免疫反应影响的研究。因此,我们在收集膳食数据的同时,还对健康的老年人(n = 40)进行了免疫分型和功能测定,然后采用综合分析方法来加深我们对老年人膳食与免疫系统相互作用的了解。我们坚信,这些新发现适合用于 IB,并将引起广大读者的浓厚兴趣。
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引用次数: 0
An integrative biology approach to understanding keratinocyte collective migration as stimulated by bioglass. 用综合生物学方法理解生物玻璃刺激的角质细胞集体迁移。
IF 2.5 4区 生物学 Q1 Medicine Pub Date : 2024-01-23 DOI: 10.1093/intbio/zyae009
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引用次数: 0
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