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Machine learning in molecular biophysics: Protein allostery, multi-level free energy simulations, and lipid phase transitions. 分子生物物理学中的机器学习:蛋白质变构、多层次自由能模拟和脂质相变。
IF 3.4 Q2 BIOPHYSICS Pub Date : 2025-02-12 eCollection Date: 2025-03-01 DOI: 10.1063/5.0248589
Qiang Cui

Machine learning (ML) techniques have been making major impacts on all areas of science and engineering, including biophysics. In this review, we discuss several applications of ML to biophysical problems based on our recent research. The topics include the use of ML techniques to identify hotspot residues in allosteric proteins using deep mutational scanning data and to analyze how mutations of these hotspots perturb co-operativity in the framework of a statistical thermodynamic model, to improve the accuracy of free energy simulations by integrating data from different levels of potential energy functions, and to determine the phase transition temperature of lipid membranes. Through these examples, we illustrate the unique value of ML in extracting patterns or parameters from complex data sets, as well as the remaining limitations. By implementing the ML approaches in the context of physically motivated models or computational frameworks, we are able to gain a deeper mechanistic understanding or better convergence in numerical simulations. We conclude by briefly discussing how the introduced models can be further expanded to tackle more complex problems.

机器学习(ML)技术已经对包括生物物理学在内的所有科学和工程领域产生了重大影响。在本文中,我们根据我们最近的研究,讨论了机器学习在生物物理问题中的几个应用。主题包括使用ML技术利用深度突变扫描数据识别变构蛋白中的热点残基,分析这些热点的突变如何在统计热力学模型框架下干扰协同作用,通过整合来自不同水平势能函数的数据来提高自由能模拟的准确性,以及确定脂质膜的相变温度。通过这些例子,我们说明了机器学习在从复杂数据集中提取模式或参数方面的独特价值,以及其他局限性。通过在物理驱动模型或计算框架的背景下实现ML方法,我们能够在数值模拟中获得更深层次的机制理解或更好的收敛性。最后,我们简要讨论了如何进一步扩展所引入的模型以解决更复杂的问题。
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引用次数: 0
Halide perovskites, a game changer for future medical imaging technology. 卤化物钙钛矿,改变未来医学成像技术的游戏规则。
IF 3.4 Q2 BIOPHYSICS Pub Date : 2025-01-22 eCollection Date: 2025-03-01 DOI: 10.1063/5.0217068
Feng Li

The accurate detection of x-rays enables broad applications in various fields, including medical radiography, safety and security screening, and nondestructive inspection. Medical imaging procedures require the x-ray detection devices operating with low doses and high efficiency to reduce radiation health risks, as well as expect the flexible or wearable ones that offer more comfortable and accurate diagnosis experiences. Recently, halide perovskites have shown promising potential in high-performance, cost-effective x-ray detection owing to their attractive features, such as strong x-ray absorption, high-mobility-lifetime product, tunable bandgap, fast response, as well as low-cost raw materials, facile processing, and excellent flexibility. In this review, we comprehensively summarize the recent advances in halide perovskite x-ray detectors and imaging, focusing on their application potential in medical imaging technology. We highlight the recent demonstrations and optimizations of halide perovskite x-ray detectors and imaging and their application in medical radiography. Finally, we conclude by pointing out the challenges of perovskite x-ray detection devices for the clinical practical applications and by sharing our perspectives on the potential solutions for driving the field forward.

x射线的精确检测使其广泛应用于各种领域,包括医学放射照相、安全和保安检查以及无损检测。医学成像程序要求x射线检测设备以低剂量和高效率运行,以减少辐射健康风险,并期望柔性或可穿戴设备提供更舒适和准确的诊断体验。近年来,卤化物钙钛矿由于具有强x射线吸收、高迁移寿命产品、可调带隙、快速响应、低成本原材料、易于加工和优异的灵活性等吸引人的特点,在高性能、低成本的x射线检测中显示出巨大的潜力。本文综述了卤化物钙钛矿x射线探测器及其成像技术的最新进展,重点介绍了卤化物钙钛矿x射线探测器及其成像技术在医学成像技术中的应用潜力。我们强调最近的演示和优化卤化物钙钛矿x射线探测器和成像及其在医学放射学中的应用。最后,我们指出了钙钛矿x射线检测设备在临床实际应用中的挑战,并分享了我们对推动该领域向前发展的潜在解决方案的看法。
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引用次数: 0
Recent advances in the tools and techniques for AI-aided diagnosis of atrial fibrillation. 人工智能辅助房颤诊断工具和技术的最新进展。
IF 3.4 Q2 BIOPHYSICS Pub Date : 2025-01-15 eCollection Date: 2025-03-01 DOI: 10.1063/5.0217416
Saiful Islam, Md Rashedul Islam, Sanjid-E-Elahi, Md Anwarul Abedin, Tansel Dökeroğlu, Mahmudur Rahman

Atrial fibrillation (AF) is recognized as a developing global epidemic responsible for a significant burden of morbidity and mortality. To counter this public health crisis, the advancement of artificial intelligence (AI)-aided tools and methodologies for the effective detection and monitoring of AF is becoming increasingly apparent. A unified strategy from the international research community is essential to develop effective intelligent tools and technologies to support the health professionals for effective surveillance and defense against AF. This review delves into the practical implications of AI-aided tools and techniques for AF detection across different clinical settings including screening, diagnosis, and ambulatory monitoring by reviewing the revolutionary research works. The key finding is that the advance in AI and its use for automatic detection of AF has achieved remarkable success, but collaboration between AI and human intelligence is required for trustworthy diagnostic of this life-threatening cardiac condition. Moreover, designing efficient and robust intelligent algorithms for onboard AF detection using portable and implementable computing devices with limited computation power and energy supply is a crucial research problem. As modern wearable devices are equipped with sophisticated embedded sensors, such as optical sensors and accelerometers, hence photoplethysmography and ballistocardiography signals could be explored as an affordable alternative to electrocardiography (ECG) signals for AF detection, particularly for the development of low-cost and miniature screening and monitoring devices.

房颤(AF)被认为是一种发展中的全球流行病,造成了严重的发病率和死亡率负担。为了应对这一公共卫生危机,人工智能(AI)辅助工具和方法在有效检测和监测房颤方面的进步正变得越来越明显。国际研究界的统一战略对于开发有效的智能工具和技术至关重要,以支持卫生专业人员有效监测和防御房颤。本文通过回顾革命性的研究工作,深入探讨了人工智能辅助工具和技术在不同临床环境下检测房颤的实际意义,包括筛查、诊断和门诊监测。关键的发现是,人工智能的进步及其在房颤自动检测中的应用取得了显著的成功,但人工智能和人类智能之间的合作需要对这种危及生命的心脏病进行可靠的诊断。此外,在有限的计算能力和能量供应下,利用便携、可实现的计算设备设计高效、鲁棒的机载自动对焦检测智能算法是一个关键的研究问题。由于现代可穿戴设备配备了复杂的嵌入式传感器,如光学传感器和加速度计,因此可以探索光电容积脉搏图和弹道心动图信号作为一种经济实惠的替代心电图(ECG)信号用于AF检测,特别是用于开发低成本和微型筛查和监测设备。
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引用次数: 0
Decoding chaperone complexes: Insights from NMR spectroscopy. 解码伴侣复合物:来自核磁共振光谱的见解。
IF 3.4 Q2 BIOPHYSICS Pub Date : 2024-12-10 eCollection Date: 2024-12-01 DOI: 10.1063/5.0233299
Shreya Ghosh, G Marius Clore

Molecular chaperones play a key role in protein homeostasis by preventing misfolding and aggregation, assisting in proper protein folding, and sometimes even disaggregating formed aggregates. Chaperones achieve this through a range of transient weak protein-protein interactions, which are difficult to study using traditional structural and biophysical techniques. Nuclear magnetic resonance (NMR) spectroscopy, however, is well-suited for studying such dynamic states and interactions. A wide range of NMR experiments have been particularly valuable in understanding the mechanisms of chaperone function, as they can characterize disordered protein structures, detect weak and nonspecific interactions involving sparsely populated states, and probe the conformational dynamics of proteins and their complexes. Recent advances in NMR have significantly enhanced our knowledge of chaperone mechanisms, especially chaperone-client interactions, despite the inherent challenges posed by the flexibility and complexity of these systems. In this review, we highlight contributions of NMR to the chaperone field, focusing on the work carried out in our laboratory, which have provided insights into how chaperones maintain function within the cellular environment and interact with various protein substrates.

分子伴侣通过防止错误折叠和聚集、协助蛋白质正确折叠,有时甚至分解已形成的聚集体,在蛋白质平衡中发挥着关键作用。分子伴侣通过一系列瞬时的弱蛋白质-蛋白质相互作用来实现这一目标,而传统的结构和生物物理技术很难对这些相互作用进行研究。然而,核磁共振(NMR)光谱非常适合研究这种动态状态和相互作用。各种核磁共振实验对了解伴侣功能的机理特别有价值,因为它们可以描述无序的蛋白质结构,检测涉及稀疏状态的微弱和非特异性相互作用,并探测蛋白质及其复合物的构象动态。尽管这些系统的灵活性和复杂性给我们带来了固有的挑战,但核磁共振的最新进展极大地增强了我们对伴侣机制的了解,尤其是伴侣与客户之间的相互作用。在这篇综述中,我们将重点介绍核磁共振对伴侣领域的贡献,重点是我们实验室开展的工作,这些工作让我们深入了解了伴侣如何在细胞环境中保持功能并与各种蛋白质底物相互作用。
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引用次数: 0
Regulation of cytoskeleton dynamics and its interplay with force in plant cells. 植物细胞的细胞骨架动力学调控及其与力的相互作用
IF 3.4 Q2 BIOPHYSICS Pub Date : 2024-11-25 eCollection Date: 2024-12-01 DOI: 10.1063/5.0201899
Zhenping Sun, Xueqing Wang, Chaoyong Peng, Liufeng Dai, Ting Wang, Yi Zhang

The plant cytoskeleton is an intricate network composed of actin filaments and microtubules. The cytoskeleton undergoes continuous dynamic changes that provide the basis for rapidly responding to intrinsic and extrinsic stimuli, including mechanical stress. Microtubules can respond to alterations of mechanical stress and reorient along the direction of maximal tensile stress in plant cells. The cytoskeleton can also generate driving force for cytoplasmic streaming, organelle movement, and vesicle transportation. In this review, we discuss the progress of how the plant cytoskeleton responds to mechanical stress. We also summarize the roles of the cytoskeleton in generating force that drive organelles and nuclear transportation in plant cells. Finally, some hypotheses concerning the link between the roles of the cytoskeleton in force response and organelle movement, as well as several key questions that remain to be addressed in the field, are highlighted.

植物细胞骨架是由肌动蛋白丝和微管组成的复杂网络。细胞骨架不断发生动态变化,为快速响应内在和外在刺激(包括机械应力)提供了基础。微管能对机械应力的变化做出反应,并沿着植物细胞中最大拉伸应力的方向重新定向。细胞骨架还能为细胞质流、细胞器运动和囊泡运输产生驱动力。在本综述中,我们将讨论植物细胞骨架如何应对机械应力的研究进展。我们还总结了细胞骨架在产生驱动植物细胞器和核运输的力方面的作用。最后,我们强调了一些关于细胞骨架在力响应和细胞器运动中的作用之间联系的假设,以及该领域仍有待解决的几个关键问题。
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引用次数: 0
AI-integrated network for RNA complex structure and dynamic prediction. 用于 RNA 复杂结构和动态预测的人工智能集成网络。
IF 3.4 Q2 BIOPHYSICS Pub Date : 2024-11-05 eCollection Date: 2024-12-01 DOI: 10.1063/5.0237319
Haoquan Liu, Chen Zhuo, Jiaming Gao, Chengwei Zeng, Yunjie Zhao

RNA complexes are essential components in many cellular processes. The functions of these complexes are linked to their tertiary structures, which are shaped by detailed interface information, such as binding sites, interface contact, and dynamic conformational changes. Network-based approaches have been widely used to analyze RNA complex structures. With their roots in the graph theory, these methods have a long history of providing insight into the static and dynamic properties of RNA molecules. These approaches have been effective in identifying functional binding sites and analyzing the dynamic behavior of RNA complexes. Recently, the advent of artificial intelligence (AI) has brought transformative changes to the field. These technologies have been increasingly applied to studying RNA complex structures, providing new avenues for understanding the complex interactions within RNA complexes. By integrating AI with traditional network analysis methods, researchers can build more accurate models of RNA complex structures, predict their dynamic behaviors, and even design RNA-based inhibitors. In this review, we introduce the integration of network-based methodologies with AI techniques to enhance the understanding of RNA complex structures. We examine how these advanced computational tools can be used to model and analyze the detailed interface information and dynamic behaviors of RNA molecules. Additionally, we explore the potential future directions of how AI-integrated networks can aid in the modeling and analyzing RNA complex structures.

RNA 复合物是许多细胞过程的重要组成部分。这些复合体的功能与其三级结构有关,而三级结构是由详细的界面信息(如结合位点、界面接触和动态构象变化)形成的。基于网络的方法已被广泛用于分析 RNA 复合物结构。这些方法源于图论,在深入了解 RNA 分子的静态和动态特性方面有着悠久的历史。这些方法在识别功能结合位点和分析 RNA 复合物的动态行为方面非常有效。最近,人工智能(AI)的出现给这一领域带来了变革。这些技术越来越多地被应用于研究 RNA 复合物结构,为了解 RNA 复合物内部复杂的相互作用提供了新的途径。通过将人工智能与传统的网络分析方法相结合,研究人员可以建立更精确的 RNA 复合物结构模型,预测其动态行为,甚至设计基于 RNA 的抑制剂。在这篇综述中,我们将介绍如何将基于网络的方法与人工智能技术相结合,以加深对 RNA 复合物结构的理解。我们将探讨如何利用这些先进的计算工具来建模和分析 RNA 分子的详细界面信息和动态行为。此外,我们还探讨了人工智能集成网络如何帮助 RNA 复杂结构建模和分析的潜在未来方向。
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引用次数: 0
Nanotechnology in retinal diseases: From disease diagnosis to therapeutic applications. 视网膜疾病中的纳米技术:从疾病诊断到治疗应用。
IF 3.4 Q2 BIOPHYSICS Pub Date : 2024-11-05 eCollection Date: 2024-12-01 DOI: 10.1063/5.0214899
Geetika Kaur, Shivantika Bisen, Nikhlesh K Singh

Nanotechnology has demonstrated tremendous promise in the realm of ocular illnesses, with applications for disease detection and therapeutic interventions. The nanoscale features of nanoparticles enable their precise interactions with retinal tissues, allowing for more efficient and effective treatments. Because biological organs are compatible with diverse nanomaterials, such as nanoparticles, nanowires, nanoscaffolds, and hybrid nanostructures, their usage in biomedical applications, particularly in retinal illnesses, has increased. The use of nanotechnology in medicine is advancing rapidly, and recent advances in nanomedicine-based diagnosis and therapy techniques may provide considerable benefits in addressing the primary causes of blindness related to retinal illnesses. The current state, prospects, and challenges of nanotechnology in monitoring nanostructures or cells in the eye and their application to regenerative ophthalmology have been discussed and thoroughly reviewed. In this review, we build on our previously published review article in 2021, where we discussed the impact of nano-biomaterials in retinal regeneration. However, in this review, we extended our focus to incorporate and discuss the application of nano-biomaterials on all retinal diseases, with a highlight on nanomedicine-based diagnostic and therapeutic research studies.

纳米技术在眼科疾病领域展现出巨大前景,可应用于疾病检测和治疗干预。纳米粒子的纳米级特征使其能够与视网膜组织产生精确的相互作用,从而实现更高效、更有效的治疗。由于生物器官与各种纳米材料(如纳米粒子、纳米线、纳米支架和混合纳米结构)兼容,它们在生物医学(尤其是视网膜疾病)中的应用日益增多。纳米技术在医学中的应用正在迅速发展,基于纳米医学的诊断和治疗技术的最新进展可能会在解决与视网膜疾病相关的主要致盲原因方面带来相当大的益处。纳米技术在监测眼部纳米结构或细胞方面的现状、前景和挑战及其在再生眼科中的应用已得到讨论和深入研究。在本综述中,我们以 2021 年发表的综述文章为基础,讨论了纳米生物材料对视网膜再生的影响。不过,在这篇综述中,我们将重点扩展到纳米生物材料在所有视网膜疾病中的应用,并重点讨论了基于纳米药物的诊断和治疗研究。
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引用次数: 0
Engineered tools to study endocrine dysfunction of pancreas. 研究胰腺内分泌功能障碍的工程工具。
IF 3.4 Q2 BIOPHYSICS Pub Date : 2024-10-22 eCollection Date: 2024-12-01 DOI: 10.1063/5.0220396
Charles G Alver, Juan Dominguez-Bendala, Ashutosh Agarwal

Pancreas, a vital organ with intricate endocrine and exocrine functions, is central to the regulation of the body's glucose levels and digestive processes. Disruptions in its endocrine functions, primarily regulated by islets of Langerhans, can lead to debilitating diseases such as diabetes mellitus. Murine models of pancreatic dysfunction have contributed significantly to the understanding of insulitis, islet-relevant immunological responses, and the optimization of cell therapies. However, genetic differences between mice and humans have severely limited their clinical translational relevance. Recent advancements in tissue engineering and microfabrication have ushered in a new era of in vitro models that offer a promising solution. This paper reviews the state-of-the-art engineered tools designed to study endocrine dysfunction of the pancreas. Islet on a chip devices that allow precise control of various culture conditions and noninvasive readouts of functional outcomes have led to the generation of physiomimetic niches for primary and stem cell derived islets. Live pancreatic slices are a new experimental tool that could more comprehensively recapitulate the complex cellular interplay between the endocrine and exocrine parts of the pancreas. Although a powerful tool, live pancreatic slices require more complex control over their culture parameters such as local oxygenation and continuous removal of digestive enzymes and cellular waste products for maintaining experimental functionality over long term. The combination of islet-immune and slice on chip strategies can guide the path toward the next generation of pancreatic tissue modeling for better understanding and treatment of endocrine pancreatic dysfunctions.

胰腺是一个具有复杂的内分泌和外分泌功能的重要器官,是调节人体血糖水平和消化过程的核心。胰腺的内分泌功能主要由朗格汉斯胰岛调节,其功能紊乱可导致糖尿病等使人衰弱的疾病。胰腺功能障碍的小鼠模型对了解胰岛炎、胰岛相关免疫反应和优化细胞疗法做出了重大贡献。然而,小鼠与人类的基因差异严重限制了它们的临床转化意义。组织工程和微细加工领域的最新进展开创了体外模型的新时代,提供了一种前景广阔的解决方案。本文回顾了为研究胰腺内分泌功能障碍而设计的最先进的工程工具。芯片上的胰岛装置可精确控制各种培养条件,并对功能结果进行无创读取,从而为原始胰岛和干细胞衍生胰岛创造了仿生龛位。活胰腺切片是一种新的实验工具,可以更全面地再现胰腺内分泌和外分泌部分之间复杂的细胞相互作用。虽然活胰腺切片是一种功能强大的工具,但需要对其培养参数进行更复杂的控制,如局部充氧、持续清除消化酶和细胞废物,以长期保持实验功能。胰岛免疫和芯片切片策略的结合可以为下一代胰腺组织建模提供指导,从而更好地理解和治疗胰腺内分泌功能障碍。
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引用次数: 0
Spatially defined microenvironment for engineering organoids. 空间限定的有机体工程微环境
IF 3.4 Q2 BIOPHYSICS Pub Date : 2024-10-18 eCollection Date: 2024-12-01 DOI: 10.1063/5.0198848
Yilan Zhang, Fukang Qi, Peng Chen, Bi-Feng Liu, Yiwei Li

In the intricately defined spatial microenvironment, a single fertilized egg remarkably develops into a conserved and well-organized multicellular organism. This observation leads us to hypothesize that stem cells or other seed cell types have the potential to construct fully structured and functional tissues or organs, provided the spatial cues are appropriately configured. Current organoid technology, however, largely depends on spontaneous growth and self-organization, lacking systematic guided intervention. As a result, the structures replicated in vitro often emerge in a disordered and sparse manner during growth phases. Although existing organoids have made significant contributions in many aspects, such as advancing our understanding of development and pathogenesis, aiding personalized drug selection, as well as expediting drug development, their potential in creating large-scale implantable tissue or organ constructs, and constructing multicomponent microphysiological systems, together with functioning at metabolic levels remains underutilized. Recent discoveries have demonstrated that the spatial definition of growth factors not only induces directional growth and migration of organoids but also leads to the formation of assembloids with multiple regional identities. This opens new avenues for the innovative engineering of higher-order organoids. Concurrently, the spatial organization of other microenvironmental cues, such as physical stresses, mechanical loads, and material composition, has been minimally explored. This review delves into the burgeoning field of organoid engineering with a focus on potential spatial microenvironmental control. It offers insight into the molecular principles, expected outcomes, and potential applications, envisioning a future perspective in this domain.

在错综复杂的空间微环境中,单个受精卵可显著发育成结构完整的多细胞生物体。这一观察结果让我们假设,只要空间线索配置得当,干细胞或其他种子细胞类型就有可能构建结构完整、功能齐全的组织或器官。然而,目前的类器官技术在很大程度上依赖于自发生长和自我组织,缺乏系统的引导干预。因此,体外复制的结构往往在生长阶段以无序和稀疏的方式出现。尽管现有的有机体在许多方面做出了重大贡献,如促进我们对发育和发病机制的了解、帮助个性化药物选择以及加快药物开发,但其在创建大规模可植入组织或器官构建体、构建多组分微观生理系统以及在新陈代谢水平上发挥作用的潜力仍未得到充分利用。最近的发现表明,生长因子的空间定义不仅能诱导器官组织的定向生长和迁移,还能形成具有多个区域特征的集合体。这为高阶有机体的创新工程开辟了新途径。与此同时,人们对其他微环境线索(如物理应力、机械负荷和材料成分)的空间组织研究还很少。本综述深入探讨了蓬勃发展的类器官工程学领域,重点关注潜在的空间微环境控制。它深入探讨了分子原理、预期结果和潜在应用,展望了这一领域的未来前景。
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引用次数: 0
Regulation of epithelial cell jamming transition by cytoskeleton and cell-cell interactions. 细胞骨架和细胞间相互作用对上皮细胞干扰转换的调控。
IF 3.4 Q2 BIOPHYSICS Pub Date : 2024-10-14 eCollection Date: 2024-12-01 DOI: 10.1063/5.0220088
Zoe D Latham, Alexandra Bermudez, Jimmy K Hu, Neil Y C Lin

Multicellular systems, such as epithelial cell collectives, undergo transitions similar to those in inert physical systems like sand piles and foams. To remodel or maintain tissue organization during development or disease, these collectives transition between fluid-like and solid-like states, undergoing jamming or unjamming transitions. While these transitions share principles with physical systems, understanding their regulation and implications in cell biology is challenging. Although cell jamming and unjamming follow physics principles described by the jamming diagram, they are fundamentally biological processes. In this review, we explore how cellular processes and interactions regulate jamming and unjamming transitions. We begin with an overview of how these transitions control tissue remodeling in epithelial model systems and describe recent findings of the physical principles governing tissue solidification and fluidization. We then explore the mechanistic pathways that modulate the jamming phase diagram axes, focusing on the regulation of cell fluctuations and geometric compatibility. Drawing upon seminal works in cell biology, we discuss the roles of cytoskeleton and cell-cell adhesion in controlling cell motility and geometry. This comprehensive view illustrates the molecular control of cell jamming and unjamming, crucial for tissue remodeling in various biological contexts.

多细胞系统,如上皮细胞集合体,会发生与沙堆和泡沫等惰性物理系统类似的转变。为了在发育或疾病过程中重塑或维持组织结构,这些集合体会在类似流体和类似固体的状态之间转换,经历干扰或非干扰转换。虽然这些转换与物理系统有着相同的原理,但要理解它们在细胞生物学中的调控和影响却很困难。虽然细胞干扰和解干扰遵循干扰图所描述的物理原理,但它们从根本上说是生物过程。在本综述中,我们将探讨细胞过程和相互作用如何调控干扰和非干扰转换。首先,我们概述了这些转换如何控制上皮模型系统中的组织重塑,并描述了最近对支配组织凝固和流化的物理原理的发现。然后,我们将重点放在细胞波动和几何相容性的调控上,探索调控凝固相图轴的机理途径。借鉴细胞生物学的开创性成果,我们讨论了细胞骨架和细胞-细胞粘附在控制细胞运动和几何方面的作用。这种全面的观点说明了细胞干扰和解除干扰的分子控制,这对各种生物环境中的组织重塑至关重要。
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引用次数: 0
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