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Mechanoregulation and function of calponin and transgelin. 钙调蛋白和转铁蛋白的机制调节和功能。
Pub Date : 2024-03-19 eCollection Date: 2024-03-01 DOI: 10.1063/5.0176784
Monica Rasmussen, J-P Jin

It is well known that chemical energy can be converted to mechanical force in biological systems by motor proteins such as myosin ATPase. It is also broadly observed that constant/static mechanical signals potently induce cellular responses. However, the mechanisms that cells sense and convert the mechanical force into biochemical signals are not well understood. Calponin and transgelin are a family of homologous proteins that participate in the regulation of actin-activated myosin motor activity. An isoform of calponin, calponin 2, has been shown to regulate cytoskeleton-based cell motility functions under mechanical signaling. The expression of the calponin 2 gene and the turnover of calponin 2 protein are both under mechanoregulation. The regulation and function of calponin 2 has physiological and pathological significance, as shown in platelet adhesion, inflammatory arthritis, arterial atherosclerosis, calcific aortic valve disease, post-surgical fibrotic peritoneal adhesion, chronic proteinuria, ovarian insufficiency, and tumor metastasis. The levels of calponin 2 vary in different cell types, reflecting adaptations to specific tissue environments and functional states. The present review focuses on the mechanoregulation of calponin and transgelin family proteins to explore how cells sense steady tension and convert the force signal to biochemical activities. Our objective is to present a current knowledge basis for further investigations to establish the function and mechanisms of calponin and transgelin in cellular mechanoregulation.

众所周知,在生物系统中,化学能可通过肌球蛋白 ATP 酶等运动蛋白转化为机械力。人们还广泛观察到,恒定/静态机械信号能有效诱导细胞反应。然而,细胞感知机械力并将其转化为生化信号的机制尚不十分清楚。钙蛋白和转铁蛋白是一个同源蛋白家族,它们参与调节肌动蛋白激活的肌球蛋白运动活性。钙调蛋白的一种异构体--钙调蛋白 2,已被证明能在机械信号作用下调节基于细胞骨架的细胞运动功能。钙调蛋白 2 基因的表达和钙调蛋白 2 蛋白的周转都受到机械调控。钙蛋白 2 的调控和功能具有生理和病理意义,如血小板粘附、炎症性关节炎、动脉粥样硬化、钙化性主动脉瓣疾病、手术后纤维化腹膜粘连、慢性蛋白尿、卵巢功能不全和肿瘤转移等。不同类型细胞中钙调蛋白 2 的水平各不相同,反映了对特定组织环境和功能状态的适应性。本综述侧重于钙调蛋白和转肽酶家族蛋白的机械调节,以探讨细胞如何感知稳定的张力并将力信号转化为生化活动。我们的目的是为进一步研究提供现有的知识基础,以确定钙蛋白和转鞘磷脂在细胞机械调节中的功能和机制。
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引用次数: 0
When art and science collide 当艺术与科学碰撞
Pub Date : 2024-03-01 DOI: 10.1063/5.0203543
Francesco Pasqualini
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引用次数: 0
Biosignal-integrated robotic systems with emerging trends in visual interfaces: A systematic review. 视觉界面新趋势下的生物信号集成机器人系统:系统综述。
Pub Date : 2024-02-21 eCollection Date: 2024-03-01 DOI: 10.1063/5.0185568
Jaeho Lee, Sina Miri, Allison Bayro, Myunghee Kim, Heejin Jeong, Woon-Hong Yeo

Human-machine interfaces (HMI) are currently a trendy and rapidly expanding area of research. Interestingly, the human user does not readily observe the interface between humans and machines. Instead, interactions between the machine and electrical signals from the user's body are obscured by complex control algorithms. The result is effectively a one-way street, wherein data is only transmitted from human to machine. Thus, a gap remains in the literature: how can information be effectively conveyed to the user to enable mutual understanding between humans and machines? Here, this paper reviews recent advancements in biosignal-integrated wearable robotics, with a particular emphasis on "visualization"-the presentation of relevant data, statistics, and visual feedback to the user. This review article covers various signals of interest, such as electroencephalograms and electromyograms, and explores novel sensor architectures and key materials. Recent developments in wearable robotics are examined from control and mechanical design perspectives. Additionally, we discuss current visualization methods and outline the field's future direction. While much of the HMI field focuses on biomedical and healthcare applications, such as rehabilitation of spinal cord injury and stroke patients, this paper also covers less common applications in manufacturing, defense, and other domains.

人机界面(HMI)目前是一个时髦且正在迅速扩展的研究领域。有趣的是,人类用户并不容易观察到人机界面。相反,机器与来自用户身体的电信号之间的互动被复杂的控制算法所掩盖。这实际上是一条单行道,数据只从人类传送到机器。因此,文献中仍然存在一个空白:如何才能有效地向用户传递信息,从而实现人机之间的相互理解?本文回顾了集成生物信号的可穿戴机器人技术的最新进展,特别强调了 "可视化"--向用户展示相关数据、统计资料和视觉反馈。这篇综述文章涵盖了脑电图和肌电图等各种相关信号,并探讨了新型传感器架构和关键材料。文章从控制和机械设计的角度探讨了可穿戴机器人技术的最新发展。此外,我们还讨论了当前的可视化方法,并概述了该领域的未来发展方向。虽然人机界面领域的大部分内容都集中在生物医学和医疗保健应用上,例如脊髓损伤和中风患者的康复,但本文也涵盖了制造业、国防和其他领域中较少见的应用。
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引用次数: 0
A life off the beaten track in biomechanics: Imperfect elasticity, cytoskeletal glassiness, and epithelial unjamming 偏离轨道的生物力学生活:不完美的弹性、细胞骨架玻璃化和上皮松动
Pub Date : 2023-12-01 DOI: 10.1063/5.0179719
Lior Atia, J. Fredberg
Textbook descriptions of elasticity, viscosity, and viscoelasticity fail to account for certain mechanical behaviors that typify soft living matter. Here, we consider three examples. First, strong empirical evidence suggests that within lung parenchymal tissues, the frictional stresses expressed at the microscale are fundamentally not of viscous origin. Second, the cytoskeleton (CSK) of the airway smooth muscle cell, as well as that of all eukaryotic cells, is more solid-like than fluid-like, yet its elastic modulus is softer than the softest of soft rubbers by a factor of 104–105. Moreover, the eukaryotic CSK expresses power law rheology, innate malleability, and fluidization when sheared. For these reasons, taken together, the CSK of the living eukaryotic cell is reminiscent of the class of materials called soft glasses, thus likening it to inert materials such as clays, pastes slurries, emulsions, and foams. Third, the cellular collective comprising a confluent epithelial layer can become solid-like and jammed, fluid-like and unjammed, or something in between. Esoteric though each may seem, these discoveries are consequential insofar as they impact our understanding of bronchospasm and wound healing as well as cancer cell invasion and embryonic development. Moreover, there are reasons to suspect that certain of these phenomena first arose in the early protist as a result of evolutionary pressures exerted by the primordial microenvironment. We have hypothesized, further, that each then became passed down virtually unchanged to the present day as a conserved core process. These topics are addressed here not only because they are interesting but also because they track the journey of one laboratory along a path less traveled by.
教科书中对弹性、粘度和粘弹性的描述未能解释软生命物质的某些典型机械行为。在此,我们考虑三个例子。首先,强有力的经验证据表明,在肺实质组织中,微观尺度上的摩擦应力从根本上说并非源于粘性。其次,气道平滑肌细胞以及所有真核细胞的细胞骨架(CSK)更像固体而非流体,但其弹性模量却比最柔软的软橡胶还要软104-105倍。此外,真核细胞的 CSK 还表现出幂律流变性、天生的延展性和剪切时的流动性。由于这些原因,综合来看,真核生物活细胞的 CSK 让人联想到被称为软玻璃的一类材料,从而将其与粘土、糊状浆液、乳液和泡沫等惰性材料相提并论。第三,由汇合的上皮细胞层组成的细胞集体可以变得像固体一样堵塞,也可以像流体一样不堵塞,或者介于两者之间。这些发现看似深奥,但却影响着我们对支气管痉挛、伤口愈合、癌细胞入侵和胚胎发育的理解。此外,我们有理由怀疑,这些现象中的某些现象最初出现在早期原生生物中,是原始微环境施加的进化压力的结果。我们还进一步假设,每种现象后来都作为一种保守的核心过程,几乎一成不变地传承至今。我们在这里讨论这些话题,不仅是因为它们很有趣,还因为它们追踪了一个实验室沿着一条鲜为人知的道路所走过的历程。
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引用次数: 0
Photoresponsive peptide materials: Spatiotemporal control of self-assembly and biological functions 光致多肽材料:自组装和生物功能的时空控制
Pub Date : 2023-12-01 DOI: 10.1063/5.0179171
K. Matsuura, H. Inaba
Peptides work as both functional molecules to modulate various biological phenomena and self-assembling artificial materials. The introduction of photoresponsive units to peptides allows the spatiotemporal remote control of their structure and function upon light irradiation. This article overviews the photoresponsive peptide design, interaction with biomolecules, and applications in self-assembling materials over the last 30 years. Peptides modified with photochromic (photoisomerizable) molecules, such as azobenzene and spiropyran, reversibly photo-controlled the binding to biomolecules and nanostructure formation through self-assembly. Photocleavable molecular units irreversibly control the functions of peptides through cleavage of the main chain and deprotection by light. Photocrosslinking between peptides or between peptides and other biomolecules enhances the structural stability of peptide assemblies and complexes. These photoresponsive peptides spatiotemporally controlled the formation and dissociation of peptide assemblies, gene expressions, protein–drug interactions, protein–protein interactions, liposome deformation and motility, cytoskeleton structure and stability, and cell functions by appropriate light irradiation. These molecular systems can be applied to photo-control biological functions, molecular robots, artificial cells, and next-generation smart drug delivery materials.
肽既可以作为调节各种生物现象的功能分子,也可以作为自组装人工材料。在肽中引入光致伸缩单元,可以在光照射下对肽的结构和功能进行时空遥控。本文概述了过去 30 年中光致多肽的设计、与生物分子的相互作用以及在自组装材料中的应用。用偶氮苯和螺吡喃等光致变色(可光异构)分子修饰的肽,可逆地通过光控与生物大分子结合,并通过自组装形成纳米结构。可光裂解分子单元通过主链的裂解和光的脱保护作用,不可逆地控制肽的功能。肽与肽之间或肽与其他生物大分子之间的光交联增强了肽集合体和复合物的结构稳定性。通过适当的光照射,这些光致肽可时空控制肽集合体的形成和解离、基因表达、蛋白质-药物相互作用、蛋白质-蛋白质相互作用、脂质体变形和运动、细胞骨架结构和稳定性以及细胞功能。这些分子系统可应用于光控生物功能、分子机器人、人工细胞和新一代智能给药材料。
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引用次数: 0
Metalation and activation of Zn2+ enzymes via early secretory pathway-resident ZNT proteins 通过早期分泌途径驻留的 ZNT 蛋白对 Zn2+ 酶进行金属化和激活
Pub Date : 2023-12-01 DOI: 10.1063/5.0176048
T. Kambe, T. Wagatsuma
Zinc (Zn2+), an essential trace element, binds to various proteins, including enzymes, transcription factors, channels, and signaling molecules and their receptors, to regulate their activities in a wide range of physiological functions. Zn2+ proteome analyses have indicated that approximately 10% of the proteins encoded by the human genome have potential Zn2+ binding sites. Zn2+ binding to the functional site of a protein (for enzymes, the active site) is termed Zn2+ metalation. In eukaryotic cells, approximately one-third of proteins are targeted to the endoplasmic reticulum; therefore, a considerable number of proteins mature by Zn2+ metalation in the early secretory pathway compartments. Failure to capture Zn2+ in these compartments results in not only the inactivation of enzymes (apo-Zn2+ enzymes), but also their elimination via degradation. This process deserves attention because many Zn2+ enzymes that mature during the secretory process are associated with disease pathogenesis. However, how Zn2+ is mobilized via Zn2+ transporters, particularly ZNTs, and incorporated in enzymes has not been fully elucidated from the cellular perspective and much less from the biophysical perspective. This review focuses on Zn2+ enzymes that are activated by Zn2+ metalation via Zn2+ transporters during the secretory process. Further, we describe the importance of Zn2+ metalation from the physiopathological perspective, helping to reveal the importance of understanding Zn2+ enzymes from a biophysical perspective.
锌(Zn2+)是人体必需的微量元素,可与多种蛋白质结合,包括酶、转录因子、通道、信号分子及其受体,调节其活动,具有广泛的生理功能。Zn2+蛋白质组分析表明,人类基因组编码的蛋白质中约有10%具有潜在的Zn2+结合位点。Zn2+结合到蛋白质的功能位点(对于酶来说是活性位点)被称为Zn2+金属化。在真核细胞中,大约三分之一的蛋白质靶向内质网;因此,相当多的蛋白质在早期分泌途径室中通过Zn2+金属化成熟。在这些区室中不能捕获Zn2+不仅会导致酶(载子Zn2+酶)失活,而且还会通过降解消除它们。这一过程值得关注,因为许多在分泌过程中成熟的Zn2+酶与疾病的发病有关。然而,Zn2+是如何通过Zn2+转运体,特别是znt被动员并结合到酶中的,从细胞的角度还没有完全阐明,更不用说从生物物理的角度了。本文综述了在分泌过程中通过Zn2+转运体被Zn2+金属化激活的Zn2+酶。此外,我们从生理病理角度描述了Zn2+金属化的重要性,有助于揭示从生物物理角度理解Zn2+酶的重要性。
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引用次数: 0
Current progress toward isogeometric modeling of the heart biophysics 心脏生物物理学等几何建模的最新进展
Pub Date : 2023-11-13 DOI: 10.1063/5.0152690
Michele Torre, Simone Morganti, Francesco S. Pasqualini, Alessandro Reali
In this paper, we review a powerful methodology to solve complex numerical simulations, known as isogeometric analysis, with a focus on applications to the biophysical modeling of the heart. We focus on the hemodynamics, modeling of the valves, cardiac tissue mechanics, and on the simulation of medical devices and treatments. For every topic, we provide an overview of the methods employed to solve the specific numerical issue entailed by the simulation. We try to cover the complete process, starting from the creation of the geometrical model up to the analysis and post-processing, highlighting the advantages and disadvantages of the methodology.
在本文中,我们回顾了一种强大的方法来解决复杂的数值模拟,被称为等几何分析,重点是应用于心脏的生物物理建模。我们专注于血流动力学,瓣膜建模,心脏组织力学,以及医疗设备和治疗的模拟。对于每个主题,我们都提供了用于解决模拟所涉及的具体数值问题的方法的概述。我们试图涵盖完整的过程,从几何模型的创建到分析和后处理,突出该方法的优点和缺点。
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引用次数: 0
Quantifying nonequilibrium dynamics and thermodynamics of cell fate decision making in yeast under pheromone induction 信息素诱导下酵母细胞命运决策的非平衡动力学和热力学定量研究
Pub Date : 2023-09-01 DOI: 10.1063/5.0157759
Sheng Li, Qiong Liu, Erkang Wang, Jin Wang
Cellular responses to pheromone in yeast can range from gene expression to morphological and physiological changes. While signaling pathways are well studied, the cell fate decision-making during cellular polar growth is still unclear. Quantifying these cellular behaviors and revealing the underlying physical mechanism remain a significant challenge. Here, we employed a hidden Markov chain model to quantify the dynamics of cellular morphological systems based on our experimentally observed time series. The resulting statistics generated a stability landscape for state attractors. By quantifying rotational fluxes as the non-equilibrium driving force that tends to disrupt the current attractor state, the dynamical origin of non-equilibrium phase transition from four cell morphological fates to a single dominant fate was identified. We revealed that higher chemical voltage differences induced by a high dose of pheromone resulted in higher chemical currents, which will trigger a greater net input and, thus, more degrees of the detailed balance breaking. By quantifying the thermodynamic cost of maintaining morphological state stability, we demonstrated that the flux-related entropy production rate provides a thermodynamic origin for the phase transition in non-equilibrium morphologies. Furthermore, we confirmed that the time irreversibility in time series provides a practical way to predict the non-equilibrium phase transition.
酵母对信息素的细胞反应可以从基因表达到形态和生理变化。虽然信号通路研究得很好,但细胞极性生长过程中细胞命运的决定仍不清楚。量化这些细胞行为并揭示潜在的物理机制仍然是一个重大挑战。在这里,我们采用隐马尔可夫链模型来量化基于我们的实验观察到的时间序列的细胞形态系统的动态。由此产生的统计数据为州吸引子创造了一个稳定的前景。通过将旋转通量量化为倾向于破坏当前吸引子状态的非平衡驱动力,确定了从四种细胞形态命运到单一优势命运的非平衡相变的动力学起源。我们发现,由高剂量信息素引起的更高的化学电压差导致更高的化学电流,这将触发更大的净输入,因此,更多程度的详细平衡被打破。通过量化维持形态状态稳定的热力学成本,我们证明了与通量相关的熵产率为非平衡形态的相变提供了热力学来源。此外,我们证实了时间序列中的时间不可逆性为预测非平衡相变提供了一种实用的方法。
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引用次数: 0
Swarming of P. aeruginosa: Through the lens of biophysics. 铜绿假单胞菌的Swarming:通过生物物理学的视角。
Pub Date : 2023-09-01 Epub Date: 2023-09-28 DOI: 10.1063/5.0128140
Jean-Louis Bru, Summer J Kasallis, Quantum Zhuo, Nina Molin Høyland-Kroghsbo, Albert Siryaporn

Swarming is a collective flagella-dependent movement of bacteria across a surface that is observed across many species of bacteria. Due to the prevalence and diversity of this motility modality, multiple models of swarming have been proposed, but a consensus on a general mechanism for swarming is still lacking. Here, we focus on swarming by Pseudomonas aeruginosa due to the abundance of experimental data and multiple models for this species, including interpretations that are rooted in biology and biophysics. In this review, we address three outstanding questions about P. aeruginosa swarming: what drives the outward expansion of a swarm, what causes the formation of dendritic patterns (tendrils), and what are the roles of flagella? We review models that propose biologically active mechanisms including surfactant sensing as well as fluid mechanics-based models that consider swarms as thin liquid films. Finally, we reconcile recent observations of P. aeruginosa swarms with early definitions of swarming. This analysis suggests that mechanisms associated with sliding motility have a critical role in P. aeruginosa swarm formation.

Swarming是细菌在表面上的集体鞭毛依赖性运动,在许多细菌物种中都可以观察到。由于这种运动模式的普遍性和多样性,已经提出了多种群集模型,但对群集的一般机制仍然缺乏共识。在这里,我们关注铜绿假单胞菌的群集,因为该物种有丰富的实验数据和多种模型,包括植根于生物学和生物物理学的解释。在这篇综述中,我们解决了关于铜绿假单胞菌群集的三个悬而未决的问题:是什么驱动了群集的向外扩展,是什么导致了树突(卷须)的形成,以及鞭毛的作用是什么?我们回顾了提出生物活性机制的模型,包括表面活性剂传感以及将蜂群视为薄液膜的基于流体力学的模型。最后,我们将最近对铜绿假单胞菌群的观察与早期对群聚的定义相一致。该分析表明,与滑动运动相关的机制在铜绿假单胞菌群的形成中起着关键作用。
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引用次数: 0
Microfluidic approaches for producing lipid-based nanoparticles for drug delivery applications 用于药物递送应用的脂基纳米颗粒的微流控方法
Pub Date : 2023-09-01 DOI: 10.1063/5.0150345
Caterina Piunti, Elisa Cimetta
The importance of drug delivery for disease treatment is supported by a vast literature and increasing ongoing clinical studies. Several categories of nano-based drug delivery systems have been considered in recent years, among which lipid-based nanomedicines, both artificial and cell-derived, remain the most approved. The best artificial systems in terms of biocompatibility and low toxicity are liposomes, as they are composed of phospholipids and cholesterol, the main components of cell membranes. Extracellular vesicles—biological nanoparticles released from cells—while resembling liposomes in size, shape, and structure, have a more complex composition with up to hundreds of different types of lipids, proteins, and carbohydrates in their membranes, as well as an internal cargo. Although nanoparticle technologies have revolutionized drug delivery by enabling passive and active targeting, increased stability, improved solubilization capacity, and reduced dose and adverse effects, the clinical translation remains challenging due to manufacturing limitations such as laborious and time-consuming procedures and high batch-to-batch variability. A sea change occurred when microfluidic strategies were employed, offering advantages in terms of precise particle handling, simplified workflows, higher sensitivity and specificity, and good reproducibility and stability over bulk methods. This review examines scientific advances in the microfluidics-mediated production of lipid-based nanoparticles for therapeutic applications. We will discuss the preparation of liposomes using both hydrodynamic focusing of microfluidic flow and mixing by herringbone and staggered baffle micromixers. Then, an overview on microfluidic approaches for producing extracellular vesicles and extracellular vesicles-mimetics for therapeutic applications will describe microfluidic extrusion, surface engineering, sonication, electroporation, nanoporation, and mixing. Finally, we will outline the challenges, opportunities, and future directions of microfluidic investigation of lipid-based nanoparticles in the clinic.
大量文献和越来越多正在进行的临床研究支持药物递送对疾病治疗的重要性。近年来,人们考虑了几种基于纳米的药物传递系统,其中基于脂质的纳米药物,无论是人造的还是细胞衍生的,仍然是最被批准的。就生物相容性和低毒性而言,脂质体是最好的人工系统,因为它们由细胞膜的主要成分磷脂和胆固醇组成。细胞外囊泡——从细胞中释放出来的生物纳米颗粒——虽然在大小、形状和结构上与脂质体相似,但其膜中含有多达数百种不同类型的脂质、蛋白质和碳水化合物,以及内部货物,其组成更为复杂。虽然纳米颗粒技术通过实现被动和主动靶向、增加稳定性、提高增溶能力、减少剂量和不良反应,彻底改变了药物输送,但由于制造限制,如费力和耗时的程序以及批次间的高可变性,临床转化仍然具有挑战性。当采用微流体策略时,发生了翻天覆地的变化,与散装方法相比,它在精确的颗粒处理、简化的工作流程、更高的灵敏度和特异性以及良好的重复性和稳定性方面具有优势。本文综述了用于治疗应用的微流体介导的脂基纳米颗粒生产的科学进展。我们将讨论利用微流体动力学聚焦和人字形和交错挡板微混合器混合制备脂质体。然后,概述了用于生产细胞外囊泡和用于治疗应用的细胞外囊泡模拟物的微流控方法,将描述微流控挤出、表面工程、超声、电穿孔、纳米穿孔和混合。最后,我们将概述脂基纳米颗粒在临床微流体研究中的挑战、机遇和未来方向。
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引用次数: 0
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