Computed and Measured Forces among Membranes, nanoparticles, and Macromolecules

我们的分子生物物理科的长期目标是建立一个实用的生物材料物理学，它测量、表征和编码管理不同种类生物分子的组织和自组装的相互作用。在一定程度上与最近NIH对纳米技术的广泛兴趣有关，我们正在利用我们对范德华力波动的经验来制定涉及碳纳米管的相互作用，不仅涉及到它们的组装，而且更重要的是作为DNA等生物聚合物的基质。我们的事业因其与物理理论的紧密联系而得到加强。通过对体内、体外和计算中揭示的不同类型相互作用的一系列测量和分析，我们正在研究DNA组件，如病毒衣壳和体外看到的组件；悬浮液中的多肽和多糖；以及脂/水液晶。在所有这些体系中，我们同时观察了堆积结构，并测量了分子间的相互作用能。 范德瓦尔斯部队： 帕塞吉亚语，波德戈尔尼克；与法语，Mkrtchian，Rajter，Ching合作 尽管范德华作用力是粘结膜和蛋白质的主要相互作用，是膜界面强大表面张力的来源，也是创造膜多层或允许膜附着在人造表面的引力，但直到现在，量子物理学家和生物物理学家才在系统地合作中对它们进行了研究。今年最大的冒险是使用了几个碳纳米管的量子力学密度泛函理论(DFT)，以计算导致它们结合在一起的力，以及作为许多材料的衬底。值得注意的是，量子化学与我们在大分子相互作用方面的专业知识相结合，使我们能够看到碳纳米管之间的扭矩和力等性质。 关键是从物理理论的元素开始，这些元素将材料的极化率与其中电荷的波动联系起来。从这一点上，我们已经能够设计实验，展示大分子组织如何对溶液性质的故意变化做出反应。因此，进展是通过结构材料的现代量子理论与揭示电磁特性的实验和测量的紧密耦合来实现的。 在目前的情况下，我们与测量吸收光谱的小组合作，以便制定和计算涉及脂类、水和离子的范德华力，以及合成结构，如碳纳米管。结果表明，溶液中离子产生的电荷涨落作用力可以改变脂膜之间的作用力。我们测量了这些力，并计算了这些系统中的范德华电荷起伏作用力。 我们还在扩展层状介质中van der Waals相互作用的Lifshitz理论方面取得了进展，如脂质多层系统，能够计算具有扩展界面的物体之间的力。其范围从实用的电绝缘子复合介质到生物膜，都可以通过延长聚合物层对生物膜的作用来实现。 体外和病毒中的分子组装 别兹鲁科夫、哈里斯、帕塞吉安、佩特拉切、波德戈尼克、劳、斯坦利、托德；格尔巴特、诺布勒、泽姆 从直接测量大分子间的作用力开始，从观察受限分子入手，以组织力作用下分子组织的统计物理为基础，发展了大分子组织的新理论和新方法。其中包括在大分子聚合物的渗透压力下或被限制在病毒衣壳的硬壁中观察到的DNA。 大量的细胞过程是由小溶质的渗透作用控制的。这些包括离子通道的门控和调节基因表达的特定和非特定DNA蛋白相互作用。分子水平的渗透传感可以探测大分子之间和大分子内的作用力。通过改变浴液中盐或中性渗透分子的浓度，我们控制渗透压。 我们最近的冒险是观察DNA从受不同盐分条件影响的衣壳中排出。膨胀压力可以变化到几十个大气压，这种压力是导致DNA最初喷出的原因。这些力可以随离子条件的不同而变化。许多病毒的一个未被认识到的特征是，这些条件可以渗透到病毒中，实际上改变了病毒内部的扩张力。在一种极端情况下，简单盐中的DNA会承受巨大的膨胀压力，并被从衣壳中排出；但在其他条件下，DNA凝聚离子可以进入衣壳，DNA可能不会处于膨胀的压力下。我们已经开始测量DNA在不同离子条件下的衣壳内的运动，并开始了解离子环境如何控制抛射。这些操作最终是否会影响病毒的传染性，这是一个值得关注且令人兴奋的问题。

With a long-term goal to build a practical physics of biological material, our Section on Molecular Biophysics measures, characterizes and codifies the interactions that govern the organization and self-assembly of different kinds of biological molecules. Connected in part with the recent NIH-wide interest in nanotechnology, we are building on our experience with van der Waals fluctuation forces to formulate interactions involving carbon nanotubes not only in their assembly but also and more important as substrates for biopolymers such as DNA. Our undertaking is strengthened by its strong connection with physical theory. Through a series of measurements and analyses of the different kinds of interactions as revealed in vivo, in vitro, and in computation, we are working with DNA assemblies such as those seen in viral capsids and in vitro; polypeptides and polysaccharides in suspension; and lipid/water liquid-crystals. In all these systems, we simultaneously observe the structure of packing as well as measure intermolecular interaction energies. - - - - - - - Van der Waals forces: Parsegian, Podgornik; in collaboration with French, Mkrtchian, Rajter, Ching Despite the fact that van der Waals forces are the dominant interaction that coheres membranes and proteins, the source of the powerful surface tension at membrane interfaces, as well as the attraction that creates membrane multilayers or allows membranes to adhere to artificial surfaces, they are only now being studied in a systematic collaboration between quantum physicists and biophysicists. The greatest adventure this year has been to use the quantum mechanical density functional theory (DFT) solved for several carbon nanotubes so as to compute the forces that cause them to cohere as well as serve as a substrate for many materials. It is remarkable that quantum chemistry combined with our expertise on macromolecular interactions is allowing us to see properties such as torque as well as force between carbon nanotubes. The key has been to begin with the elements of physical theory that relate the polarizability of materials to the fluctuations of charges within them. From this we have been able to design experiments that show how macromolecular organization responds to deliberate changes in solution properties. Progress is thus through a tight coupling of modern quantum theory of structured materials coupled with experiments and measurements that reveal electromagnetic properties. In the present instance, we have teamed with groups that measure absorption spectra in order to formulate and to compute van der Waals forces involving lipids, water, and ions, as well as synthetic structures such as carbon nanotubes. The results have shown how charge fluctuation forces conferred by ions in solution can modify forces between lipid membranes. We have measured those forces as well as computed van der Waals charge fluctuation forces in those same systems. We also progressed in extending the Lifshitz theory of van der Waals interactions in stratified media like lipid multilamellar systems to be able to compute forces between bodies with extended interfaces. These can range from the practical the composite media of electric insulators to the biological the action of extended polymer layers on biological membranes. - - - - - - - Molecular assembly in vitro and in viro Bezrukov, Harries, Parsegian, Petrache, Podgornik, Rau, Stanley, Todd; Gelbart, Knobler, Zemb Beginning with direct measurements of forces between large molecules, proceeding with observations of molecules under confinement, building on the statistical physics of molecular organization under the action of organizing forces, we have developed new theories and new methods of macromolecular organization. Among these are the observations of DNA under the osmotic stress of large polymers or confined within the hard walls of a virus capsid. A remarkable number of cellular processes are controlled by the osmotic action of small solutes. These include gating of ionic channels and specific versus non-specific DNAprotein interactions regulating gene expression. Osmotic sensing at the molecular level can probe the forces acting between and within macromolecules. By varying the salt or neutral osmolyte concentration in the bathing solution, we control osmotic pressure. Our most recent adventures have been to observe the ejection of DNA from capsids that subject to different salt conditions. Expansive pressures can vary up to many tens of atmospheres, a pressure that is responsible for initial ejection of DNA. These forces can be varied by ionic conditions. An unrecognized feature of many viruses is that these conditions can penetrate the virus and in fact modify the expansive force within. At one extreme, DNA in simple salts will be under great pressure to expand and be ejected from the capsid; but under other conditions, where DNA condensing ions can enter the capsid, DNA can be under no expansive pressure. We have begun to measure the motion of DNA within capsids subject to different ionic conditions and begun to see how ejection might be controlled by ionic surroundings. Whether these manipulations ultimately affect viral infectivity is a worthwhile and exciting question.