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The biophysics of superoxide dismutase-1 and amyotrophic lateral sclerosis 超氧化物歧化酶-1与肌萎缩侧索硬化症的生物物理学
IF 6.1 2区 生物学 Q1 BIOPHYSICS Pub Date : 2019-11-25 DOI: 10.1017/S003358351900012X
G. Wright, S. Antonyuk, S. Hasnain
Abstract Few proteins have come under such intense scrutiny as superoxide dismutase-1 (SOD1). For almost a century, scientists have dissected its form, function and then later its malfunction in the neurodegenerative disease amyotrophic lateral sclerosis (ALS). We now know SOD1 is a zinc and copper metalloenzyme that clears superoxide as part of our antioxidant defence and respiratory regulation systems. The possibility of reduced structural integrity was suggested by the first crystal structures of human SOD1 even before deleterious mutations in the sod1 gene were linked to the ALS. This concept evolved in the intervening years as an impressive array of biophysical studies examined the characteristics of mutant SOD1 in great detail. We now recognise how ALS-related mutations perturb the SOD1 maturation processes, reduce its ability to fold and reduce its thermal stability and half-life. Mutant SOD1 is therefore predisposed to monomerisation, non-canonical self-interactions, the formation of small misfolded oligomers and ultimately accumulation in the tell-tale insoluble inclusions found within the neurons of ALS patients. We have also seen that several post-translational modifications could push wild-type SOD1 down this toxic pathway. Recently we have come to view ALS as a prion-like disease where both the symptoms, and indeed SOD1 misfolding itself, are transmitted to neighbouring cells. This raises the possibility of intervention after the initial disease presentation. Several small-molecule and biologic-based strategies have been devised which directly target the SOD1 molecule to change the behaviour thought to be responsible for ALS. Here we provide a comprehensive review of the many biophysical advances that sculpted our view of SOD1 biology and the recent work that aims to apply this knowledge for therapeutic outcomes in ALS.
很少有蛋白质像超氧化物歧化酶-1 (SOD1)那样受到如此严格的审查。近一个世纪以来,科学家们一直在研究它的形态、功能,以及后来它在神经退行性疾病肌萎缩性侧索硬化症(ALS)中的功能失调。我们现在知道SOD1是一种锌和铜金属酶,作为我们抗氧化防御和呼吸调节系统的一部分,它可以清除超氧化物。甚至在SOD1基因的有害突变与ALS相关之前,人类SOD1的第一个晶体结构就表明了结构完整性降低的可能性。随着一系列令人印象深刻的生物物理研究对SOD1突变体特征的详细研究,这一概念在这期间不断发展。我们现在认识到与als相关的突变如何扰乱SOD1的成熟过程,降低其折叠能力,降低其热稳定性和半衰期。因此,突变的SOD1易于单体化、非规范的自我相互作用、形成小的错误折叠的低聚物,并最终在ALS患者神经元中发现的不溶性包涵体中积累。我们还发现,一些翻译后修饰可以推动野生型SOD1沿着这条毒性途径前进。最近,我们开始将ALS视为一种朊病毒样疾病,其症状和SOD1错误折叠本身都会传播给邻近的细胞。这增加了在最初疾病出现后进行干预的可能性。一些小分子和基于生物的策略已经被设计出来,它们直接针对SOD1分子来改变被认为是导致ALS的行为。在这里,我们提供了许多生物物理学进展的全面回顾,这些进展塑造了我们对SOD1生物学的看法,以及最近旨在将这些知识应用于ALS治疗结果的工作。
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引用次数: 36
The behavior of ions in water is controlled by their water affinity 离子在水中的行为受其亲水性控制
IF 6.1 2区 生物学 Q1 BIOPHYSICS Pub Date : 2019-11-18 DOI: 10.1017/S0033583519000106
K. D. Collins
Abstract The strong, long-range electrostatic forces described by Coulomb's law disappear for ions in water, and the behavior of these ions is instead controlled by their water affinity – a weak, short-range force which arises from their charge density. This was established experimentally in the mid-1980s by size-exclusion chromatography on carefully calibrated Sephadex® G-10 (which measures the effective volume and thus the water affinity of an ion) and by neutron diffraction with isotopic substitution (which measures the density and orientation of water molecules near the diffracting ion and thus its water affinity). These conclusions have been confirmed more recently by molecular dynamics simulations, which explicitly model each individual water molecule. This surprising change in force regime occurs because the oppositely charged ions in aqueous salt solutions exist functionally as ion pairs (separated by 0, 1 or 2 water molecules) as has now been shown by dielectric relaxation spectroscopy; this cancels out the strong long-range electrostatic forces and allows the weak, short-range water affinity effects to come to the fore. This microscopic structure of aqueous salt solutions is not captured by models utilizing a macroscopic dielectric constant. Additionally, the Law of Matching Water Affinity, first described in 1997 and 2004, establishes that contact ion pair formation is controlled by water affinity and is a major determinant of the solubility of charged species since only a net neutral species can change phases.
库仑定律所描述的强的、远距离的静电力对离子在水中消失了,而这些离子的行为是由它们的亲水性控制的——一种由它们的电荷密度产生的弱的、短程的力。这是在20世纪80年代中期通过仔细校准的Sephadex®G-10(测量有效体积,从而测量离子的亲水性)和同位素取代的中子衍射(测量衍射离子附近水分子的密度和取向,从而测量其亲水性)通过实验建立的。这些结论最近得到了分子动力学模拟的证实,该模拟明确地模拟了每个单独的水分子。这种令人惊讶的力的变化发生是因为盐水溶液中带相反电荷的离子以离子对的形式存在(由0,1或2个水分子分开),这已经被介电弛豫光谱所证明;这抵消了强大的远程静电力,使弱的、近距离的亲水性效应脱颖而出。利用宏观介电常数的模型无法捕捉到盐水溶液的这种微观结构。此外,1997年和2004年首次描述的匹配亲水性定律(Law of Matching Water Affinity)表明,接触离子对的形成是由亲水性控制的,并且是带电物质溶解度的主要决定因素,因为只有净中性物质才能改变相。
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引用次数: 29
Regulation of cell adhesion: a collaborative effort of integrins, their ligands, cytoplasmic actors, and phosphorylation 细胞粘附的调控:整合素、其配体、细胞质行为体和磷酸化的协同作用
IF 6.1 2区 生物学 Q1 BIOPHYSICS Pub Date : 2019-11-11 DOI: 10.1017/S0033583519000088
C. Gahmberg, M. Grönholm, Sudarrshan Madhavan, Farhana Jahan, Esa T Mikkola, Larisa Viazmina, E. Koivunen
Abstract Integrins are large heterodimeric type 1 membrane proteins expressed in all nucleated mammalian cells. Eighteen α-chains and eight β-chains can combine to form 24 different integrins. They are cell adhesion proteins, which bind to a large variety of cellular and extracellular ligands. Integrins are required for cell migration, hemostasis, translocation of cells out from the blood stream and further movement into tissues, but also for the immune response and tissue morphogenesis. Importantly, integrins are not usually active as such, but need activation to become adhesive. Integrins are activated by outside-in activation through integrin ligand binding, or by inside-out activation through intracellular signaling. An important question is how integrin activity is regulated, and this topic has recently drawn much attention. Changes in integrin affinity for ligand binding are due to allosteric structural alterations, but equally important are avidity changes due to integrin clustering in the plane of the plasma membrane. Recent studies have partially solved how integrin cell surface structures change during activation. The integrin cytoplasmic domains are relatively short, but by interacting with a variety of cytoplasmic proteins in a regulated manner, the integrins acquire a number of properties important not only for cell adhesion and movement, but also for cellular signaling. Recent work has shown that specific integrin phosphorylations play pivotal roles in the regulation of integrin activity. Our purpose in this review is to integrate the present knowledge to enable an understanding of how cell adhesion is dynamically regulated.
整合素是在所有有核哺乳动物细胞中表达的大型异二聚体1型膜蛋白。18条α-链和8条β-链可以结合形成24种不同的整合素。它们是细胞粘附蛋白,与多种细胞和细胞外配体结合。整合素是细胞迁移、止血、细胞从血流中移位和进一步移动到组织中所必需的,也是免疫反应和组织形态发生所必需的。重要的是,整合素通常不具有活性,但需要激活才能具有粘附性。整合素通过整合素配体结合由外而内激活,或通过细胞内信号传导由内而外激活。一个重要的问题是如何调节整合素的活性,这一话题最近引起了人们的广泛关注。整合素对配体结合的亲和力变化是由于变构结构的改变,但同样重要的是由于整合素在质膜平面上聚集而引起的亲和力变化。最近的研究已经部分解决了整合素细胞在激活过程中表面结构的变化。整合素细胞质结构域相对较短,但通过与多种细胞质蛋白以受调节的方式相互作用,整合素获得了许多重要的特性,不仅对细胞粘附和运动重要,而且对细胞信号传导也很重要。最近的研究表明,特定的整合素磷酸化在整合素活性的调节中起着关键作用。我们在这篇综述中的目的是整合现有的知识,使人们能够理解细胞粘附是如何动态调节的。
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引用次数: 18
Navigating at night: fundamental limits on the sensitivity of radical pair magnetoreception under dim light 夜间导航:昏暗光线下基对磁接收灵敏度的基本限制
IF 6.1 2区 生物学 Q1 BIOPHYSICS Pub Date : 2019-10-22 DOI: 10.1017/S0033583519000076
Hamish G. Hiscock, Tom W. Hiscock, Tom W. Hiscock, D. Kattnig, T. Scrivener, Alan M. Lewis, D. Manolopoulos, P. Hore
Abstract Night-migratory songbirds appear to sense the direction of the Earth's magnetic field via radical pair intermediates formed photochemically in cryptochrome flavoproteins contained in photoreceptor cells in their retinas. It is an open question whether this light-dependent mechanism could be sufficiently sensitive given the low-light levels experienced by nocturnal migrants. The scarcity of available photons results in significant uncertainty in the signal generated by the magnetoreceptors distributed around the retina. Here we use results from Information Theory to obtain a lower bound estimate of the precision with which a bird could orient itself using only geomagnetic cues. Our approach bypasses the current lack of knowledge about magnetic signal transduction and processing in vivo by computing the best-case compass precision under conditions where photons are in short supply. We use this method to assess the performance of three plausible cryptochrome-derived flavin-containing radical pairs as potential magnetoreceptors.
夜游鸣禽似乎通过视网膜感光细胞中隐色素黄蛋白中光化学形成的自由基对中间体来感知地球磁场的方向。考虑到夜间迁徙者所经历的低光照水平,这种依赖光的机制是否足够敏感,这是一个悬而未决的问题。可用光子的稀缺性导致分布在视网膜周围的磁感受器产生的信号具有显著的不确定性。在这里,我们使用信息论的结果来获得精度的下限估计,鸟类可以仅使用地磁线索来定位自己。我们的方法通过计算光子短缺条件下的最佳罗盘精度,绕过了目前缺乏关于体内磁信号转导和处理的知识。我们使用这种方法来评估三种似是而非的隐色素衍生的含黄素自由基对作为潜在磁受体的性能。
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引用次数: 12
Tracking RNA with light: selection, structure, and design of fluorescence turn-on RNA aptamers 用光跟踪RNA:荧光开启RNA适体的选择、结构和设计
IF 6.1 2区 生物学 Q1 BIOPHYSICS Pub Date : 2019-08-19 DOI: 10.1017/S0033583519000064
R. Trachman, A. Ferré-D’Amaré
Abstract Fluorescence turn-on aptamers, in vitro evolved RNA molecules that bind conditional fluorophores and activate their fluorescence, have emerged as RNA counterparts of the fluorescent proteins. Turn-on aptamers have been selected to bind diverse fluorophores, and they achieve varying degrees of specificity and affinity. These RNA–fluorophore complexes, many of which exceed the brightness of green fluorescent protein and their variants, can be used as tags for visualizing RNA localization and transport in live cells. Structure determination of several fluorescent RNAs revealed that they have diverse, unrelated overall architectures. As most of these RNAs activate the fluorescence of their ligands by restraining their photoexcited states into a planar conformation, their fluorophore binding sites have in common a planar arrangement of several nucleobases, most commonly a G-quartet. Nonetheless, each turn-on aptamer has developed idiosyncratic structural solutions to achieve specificity and efficient fluorescence turn-on. The combined structural diversity of fluorophores and turn-on RNA aptamers has already produced combinations that cover the visual spectrum. Further molecular evolution and structure-guided engineering is likely to produce fluorescent tags custom-tailored to specific applications.
荧光开启适体,在体外进化的RNA分子结合条件荧光团并激活其荧光,已经成为荧光蛋白的RNA对应物。开启适配体已被选择来结合不同的荧光团,它们具有不同程度的特异性和亲和力。这些RNA -荧光团复合物,其中许多超过绿色荧光蛋白及其变体的亮度,可以用作可视化RNA在活细胞中的定位和运输的标签。对几种荧光rna的结构测定表明,它们具有不同的、不相关的总体结构。由于大多数这些rna通过将其光激发态限制为平面构象来激活其配体的荧光,因此它们的荧光基团结合位点共同具有几个核碱基的平面排列,最常见的是g -四重奏。尽管如此,每个开启适体已经发展出特殊的结构解决方案,以实现特异性和有效的荧光开启。荧光团的结构多样性和开启RNA适体的组合已经产生了覆盖视觉光谱的组合。进一步的分子进化和结构引导工程可能会产生为特定应用量身定制的荧光标签。
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引用次数: 28
Dynamics of proteins in solution 溶液中蛋白质的动力学
IF 6.1 2区 生物学 Q1 BIOPHYSICS Pub Date : 2019-06-13 DOI: 10.1017/S0033583519000027
M. Grimaldo, F. Roosen‐Runge, Fajun Zhang, F. Schreiber, T. Seydel
Abstract The dynamics of proteins in solution includes a variety of processes, such as backbone and side-chain fluctuations, interdomain motions, as well as global rotational and translational (i.e. center of mass) diffusion. Since protein dynamics is related to protein function and essential transport processes, a detailed mechanistic understanding and monitoring of protein dynamics in solution is highly desirable. The hierarchical character of protein dynamics requires experimental tools addressing a broad range of time- and length scales. We discuss how different techniques contribute to a comprehensive picture of protein dynamics, and focus in particular on results from neutron spectroscopy. We outline the underlying principles and review available instrumentation as well as related analysis frameworks.
蛋白质在溶液中的动力学包括多种过程,如主链和侧链波动,结构域间运动,以及全局旋转和平移(即质心)扩散。由于蛋白质动力学与蛋白质功能和基本运输过程有关,因此对溶液中蛋白质动力学的详细机制理解和监测是非常必要的。蛋白质动力学的层次特征要求实验工具处理广泛的时间和长度尺度。我们讨论了不同的技术如何有助于蛋白质动力学的全面图景,并特别关注中子光谱学的结果。我们概述了基本原则,并回顾了可用的仪器以及相关的分析框架。
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引用次数: 52
The theory of frame ordering: observing motions in calmodulin complexes. 框架有序理论:观察钙调素复合物的运动。
IF 6.1 2区 生物学 Q1 BIOPHYSICS Pub Date : 2019-04-03 DOI: 10.1017/S0033583519000015
Edward James d'Auvergne, Christian Griesinger

Large scale functional motions of molecules are studied experimentally using numerous molecular and biophysics techniques, the data from which are subsequently interpreted using diverse models of Brownian molecular dynamics. To unify all rotational physics techniques and motional models, the frame order tensor - a universal statistical mechanics theory based on the rotational ordering of rigid body frames - is herein formulated. The frame ordering is the fundamental physics that governs how motions modulate rotational molecular physics and it defines the properties and maximum information content encoded in the observable physics. Using the tensor to link residual dipolar couplings and pseudo-contact shifts, two distinct information-rich and atomic-level biophysical measurements from the field of nuclear magnetic resonance spectroscopy, to a number of basic mechanical joint models, a highly dynamic state of calmodulin (CaM) bound to a target peptide in a tightly closed conformation was observed. Intra- and inter-domain motions reveal the CaM complex to be entropically primed for peptide release.

分子的大尺度功能运动实验研究使用了许多分子和生物物理学技术,从这些数据随后解释使用不同的布朗分子动力学模型。为了统一所有旋转物理技术和运动模型,本文建立了基于刚体框架旋转有序的通用统计力学理论——框架阶张量。框架排序是控制运动如何调节旋转分子物理的基本物理,它定义了可观察物理中编码的属性和最大信息内容。利用张量将残差偶极耦合和伪接触位移这两种不同的信息丰富的原子水平的生物物理测量从核磁共振波谱学领域连接到一些基本的机械关节模型,观察到钙调素(CaM)以紧密封闭的构象结合到靶肽的高度动态状态。结构域内和结构域间的运动揭示了CaM复合体是为肽释放熵启动的。
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引用次数: 0
Oxygenic photosynthesis: history, status and perspective. 氧光合作用的历史、现状与展望
IF 6.1 2区 生物学 Q1 BIOPHYSICS Pub Date : 2019-01-01 DOI: 10.1017/S0033583518000112
Wolfgang Junge

Cyanobacteria and plants carry out oxygenic photosynthesis. They use water to generate the atmospheric oxygen we breathe and carbon dioxide to produce the biomass serving as food, feed, fibre and fuel. This paper scans the emergence of structural and mechanistic understanding of oxygen evolution over the past 50 years. It reviews speculative concepts and the stepped insight provided by novel experimental and theoretical techniques. Driven by sunlight photosystem II oxidizes the catalyst of water oxidation, a hetero-metallic Mn4CaO5(H2O)4 cluster. Mn3Ca are arranged in cubanoid and one Mn dangles out. By accumulation of four oxidizing equivalents before initiating dioxygen formation it matches the four-electron chemistry from water to dioxygen to the one-electron chemistry of the photo-sensitizer. Potentially harmful intermediates are thereby occluded in space and time. Kinetic signatures of the catalytic cluster and its partners in the photo-reaction centre have been resolved, in the frequency domain ranging from acoustic waves via infra-red to X-ray radiation, and in the time domain from nano- to milli-seconds. X-ray structures to a resolution of 1.9 Å are available. Even time resolved X-ray structures have been obtained by clocking the reaction cycle by flashes of light and diffraction with femtosecond X-ray pulses. The terminal reaction cascade from two molecules of water to dioxygen involves the transfer of four electrons, two protons, one dioxygen and one water. A rigorous mechanistic analysis is challenging because of the kinetic enslaving at millisecond duration of six partial reactions (4e-, 1H+, 1O2). For the time being a peroxide-intermediate in the reaction cascade to dioxygen has been in focus, both experimentally and by quantum chemistry. Homo sapiens has relied on burning the products of oxygenic photosynthesis, recent and fossil. Mankind's total energy consumption amounts to almost one-fourth of the global photosynthetic productivity. If the average power consumption equalled one of those nations with the highest consumption per capita it was four times greater and matched the total productivity. It is obvious that biomass should be harvested for food, feed, fibre and platform chemicals rather than for fuel.

蓝藻和植物进行含氧光合作用。它们利用水来产生我们呼吸的大气中的氧气,利用二氧化碳来生产作为食物、饲料、纤维和燃料的生物质。本文回顾了近50年来对氧演化的结构和机理的认识。它回顾了投机性的概念和新的实验和理论技术提供的阶梯洞察力。在阳光的驱动下,光系统II氧化了水氧化催化剂Mn4CaO5(H2O)4簇。Mn3Ca呈立方体排列,一个Mn悬垂出来。通过在启动双氧形成之前四个氧化当量的积累,它将从水到双氧的四电子化学与光敏剂的单电子化学相匹配。因此,潜在有害的中间体在空间和时间上被封锁。催化团簇及其在光反应中心的伙伴的动力学特征已经被解决,在频域范围从声波到红外到x射线辐射,在时域从纳米到毫秒。分辨率为1.9 Å的x射线结构是可用的。甚至时间分辨的x射线结构已获得计时的反应周期的闪光和衍射与飞秒x射线脉冲。从两个水分子到双氧分子的末端反应包括四个电子、两个质子、一个双氧分子和一个水分子的转移。由于六个部分反应(4e-, 1H+, 1O2)在毫秒时间内的动力学奴役,严格的机理分析是具有挑战性的。目前,在实验和量子化学中,二级氧化反应中的过氧化物中间体一直是人们关注的焦点。智人依靠燃烧含氧光合作用的产物,无论是近代的还是化石的。人类的总能源消耗几乎占全球光合生产力的四分之一。如果平均用电量相当于人均用电量最高的国家之一,那么它是人均用电量最高的国家的四倍,并与总生产力相匹配。很明显,生物质的收获应该作为食物、饲料、纤维和平台化学品,而不是作为燃料。
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引用次数: 48
Development of CRISPR-Cas systems for genome editing and beyond CRISPR-Cas系统在基因组编辑及其他领域的发展
IF 6.1 2区 生物学 Q1 BIOPHYSICS Pub Date : 2019-01-01 DOI: 10.1017/S0033583519000052
F. Zhang
Abstract The development of clustered regularly interspaced short-palindromic repeat (CRISPR)-Cas systems for genome editing has transformed the way life science research is conducted and holds enormous potential for the treatment of disease as well as for many aspects of biotechnology. Here, I provide a personal perspective on the development of CRISPR-Cas9 for genome editing within the broader context of the field and discuss our work to discover novel Cas effectors and develop them into additional molecular tools. The initial demonstration of Cas9-mediated genome editing launched the development of many other technologies, enabled new lines of biological inquiry, and motivated a deeper examination of natural CRISPR-Cas systems, including the discovery of new types of CRISPR-Cas systems. These new discoveries in turn spurred further technological developments. I review these exciting discoveries and technologies as well as provide an overview of the broad array of applications of these technologies in basic research and in the improvement of human health. It is clear that we are only just beginning to unravel the potential within microbial diversity, and it is quite likely that we will continue to discover other exciting phenomena, some of which it may be possible to repurpose as molecular technologies. The transformation of mysterious natural phenomena to powerful tools, however, takes a collective effort to discover, characterize, and engineer them, and it has been a privilege to join the numerous researchers who have contributed to this transformation of CRISPR-Cas systems.
用于基因组编辑的聚集规则间隔短回文重复(CRISPR)-Cas系统的发展已经改变了生命科学研究的进行方式,并且在疾病治疗以及生物技术的许多方面具有巨大的潜力。在这里,我就CRISPR-Cas9在该领域更广泛的背景下用于基因组编辑的发展提供了个人观点,并讨论了我们发现新型Cas效应物并将其开发成额外的分子工具的工作。cas9介导的基因组编辑的初步演示启动了许多其他技术的发展,启用了新的生物学探究线,并推动了对天然CRISPR-Cas系统的更深入研究,包括发现新型CRISPR-Cas系统。这些新发现反过来又刺激了进一步的技术发展。我回顾了这些令人兴奋的发现和技术,并概述了这些技术在基础研究和改善人类健康方面的广泛应用。很明显,我们只是刚刚开始揭示微生物多样性的潜力,很有可能我们会继续发现其他令人兴奋的现象,其中一些可能会被重新利用为分子技术。然而,将神秘的自然现象转化为强大的工具需要集体的努力来发现,表征和设计它们,我很荣幸能够加入众多为CRISPR-Cas系统的这种转化做出贡献的研究人员。
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引用次数: 82
Controlling the movement of molecules 控制分子的运动
IF 6.1 2区 生物学 Q1 BIOPHYSICS Pub Date : 2019-01-01 DOI: 10.1017/S0033583519000040
R. Langer
Abstract The ability to control the movement of molecules is both fascinating scientifically as well as being critically important to the well-being of our planet and its people. In particular, the sustained release of molecules over prolonged periods at controlled rates has had and will continue to have enormous implications for the delivery of substances in medicine, agriculture, the environment, nutrition, aquaculture, household consumer products, and numerous other areas. This field is advancing at a rapidly accelerating pace. In this article, I largely discuss our own work, starting 45 years ago, in enabling the controlled release of macromolecules from biocompatible polymers. I also discuss the synthesis of novel materials to affect molecular movement and I then examine external approaches for controlling the movement of molecules through materials, using forces such as electric, acoustic, and magnetic fields. I further discuss approaches for controlling molecular movement through physiologic barriers, such as the skin, lung, and intestine. Finally, I outline several future areas of this field, including how it can affect the developing world, the ability to control the movement of molecules into mammalian cells, and the design of intelligent approaches to control molecular delivery.
控制分子运动的能力不仅在科学上令人着迷,而且对我们这个星球及其人民的福祉至关重要。特别是,分子在长时间内以可控的速率持续释放,已经并将继续对医药、农业、环境、营养、水产养殖、家用消费品和许多其他领域的物质输送产生巨大影响。这一领域正在快速发展。在这篇文章中,我主要讨论了我们自己的工作,从45年前开始,使大分子从生物相容性聚合物中可控释放。我还讨论了影响分子运动的新材料的合成,然后我研究了通过材料控制分子运动的外部方法,使用诸如电场、声学和磁场等力。我进一步讨论了通过生理屏障(如皮肤、肺和肠)控制分子运动的方法。最后,我概述了该领域未来的几个领域,包括它如何影响发展中国家,控制分子进入哺乳动物细胞的能力,以及控制分子传递的智能方法的设计。
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引用次数: 9
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