Functional Biomolecular Liquids

设计具有小规模（纳米）结构并结合多个组件的新材料有望导致传感、电子、催化和医学领域新技术的发展。这些材料很难合成，一种新的方法是使用被称为蛋白质的大型生物分子作为活性成分。蛋白质是由长链氨基酸组成的，这些氨基酸折叠在一起形成复杂的三维结构。在人体中，蛋白质执行各种各样的任务（或功能），从肌肉中的氧气结合（由肌红蛋白执行）到血液中的铁储存（铁蛋白），如果这些特性可以转移到合成材料中，那将是有利的。蛋白质最常见的形式是水溶液中的分散体或干粉，值得注意的是，直到最近，纯液相中的蛋白质还不存在，也就是说，加热干燥的蛋白粉不会使其融化。从本质上讲，这意味着有一个缺失的阶段的生物物质尚未被发现。纯液体蛋白相的缺失是由于蛋白质分子的相对较大的分子尺寸（纳米级），这是一个有趣的现象，在纳米颗粒中也可以看到。这种情况的出现是因为材料的液相是由相互吸引的分子间力稳定的，这种力在比单个分子大小大得多的距离上起作用。然而，蛋白质的情况并非如此，因为它们的结构与它们之间的力的范围相比很大。从本质上讲，蛋白质分子在固相中是如此紧密地结合在一起，以至于加热不会使它们融化，而是会破坏它们的分子结构，导致分解。我的研究目的是设计一种通用的方法，通过增加有吸引力的蛋白质-蛋白质相互作用的范围来获得缺失的蛋白质液相。为了做到这一点，我将人工（合成）聚合物表面活性剂分子附着在蛋白质表面，以产生具有长卷须的蛋白质分子，这些蛋白质分子可以与更远距离的其他蛋白质分子相互作用。这些聚合物表面活性剂分子带负电荷，只附着在蛋白质表面的正电荷基团上。因此，有必要首先用化学方法改变蛋白质分子的表面，使它们带更多的正电荷，这样就可以附着足够的聚合物表面活性剂分子。在我的初步研究中，我用这种方法生产了铁蛋白和肌红蛋白的液体，它们不含水，在室温下融化。真正令人震惊的是，尽管蛋白质分子已经进化到可以在水环境中工作，但它们在纯液相中的结构似乎并没有改变，而在肌红蛋白的例子中，蛋白质仍然可以结合氧气。我提出的工作可以让我运用我在生物化学，材料科学和物理化学方面的知识来开发一类新的混合生物液体，我打算开发这种新的方法来生产各种不同功能的液体蛋白质。在每种情况下，我都会研究液体的分子结构，以及它们的组成和特性，如粘度，我也会测试蛋白质的功能。这不仅将提供一系列新的活性液体，而且将有助于理解水对蛋白质结构和功能的重要性。最后，一旦我了解了这些系统是如何工作的，我就会利用这些结果来开发基于液体蛋白质的新型材料。例如，我打算开发新的生物传感器，用于检测一氧化碳等有毒气体，或者在伤口愈合过程中为伤口提供氧气的活性伤口敷料。

Designing new materials that have small-scale (nanometre) structures and combine multiple components is expected to lead to the development of new technology in areas of sensing, electronics, catalysis and medicine. These materials can be difficult to synthesise, and a new approach is to use large biological molecules known as proteins as an active component. Proteins are made up of long chains of amino acids that fold upon themselves to form complex 3D structures. In the body, proteins perform a wide variety of tasks (or functions) from the binding of oxygen in muscles (which is performed by the protein myoglobin), to the storage of iron in the blood (ferritin), and it would be advantageous if these properties could be transferred to a synthetic material. Proteins are most commonly found either as dispersions in aqueous solutions or as dry powders, and it is fascinating to note that till recently, proteins in the pure liquid phase did not exist, i.e. heating a dry protein powder will not cause it to melt. In essence, this means that there was a missing phase of biological matter that was yet to be discovered. The absence of a pure liquid protein phase results from the relatively large molecular dimensions (nanoscale) of the protein molecule, and is an intriguing phenomenon that is also seen with nanoparticles. The situation arises because the liquid phase of a material is stabilized by attractive inter-molecular forces that act over distances that are considerably larger than the size of the individual molecules. This is not the case for proteins however, as their structures are large compared with the range of the forces between them. In essence, the protein molecules are so firmly held together in the solid phase that heating would not make them melt, but rather, would destroy their molecular structure, resulting in decomposition. The aim of my research is to design a universal approach to access the missing liquid phase of proteins by increasing the range of the attractive protein-protein interactions. To do this I will attach artificial (synthetic) polymer surfactant molecules to the proteins' surfaces to produce protein molecules with long tendrils that can interact with other protein molecules over longer distances. These polymer surfactant molecules are negatively charged, and only attach to positively charged groups on the protein surface. Hence it will be necessary to first chemically alter the surface of the protein molecules to make them more positively charged, so that enough of the polymer surfactant molecules can be attached. In my preliminary studies I used this approach to produce liquids of ferritin and myoglobin, which contained no water and melted near room temperature. What was truly astounding is that even though the protein molecules have evolved to operate in aqueous environments, their structures in the pure liquid phase appeared not to have changed, and in the case of myoglobin, the protein could still bind oxygen. My proposed work allows me to apply my knowledge of biochemistry, materials science and physical chemistry to develop a new class of hybrid biological liquids, and I intend to develop this new approach to produce a wide range of liquid proteins with different functions. In each case I will investigate the molecular structure of the liquids, as well as their composition and properties such as viscosity, and I will also test the protein for function. This will not only provide a range of new active liquids, but will aid in the understanding of how important water is for protein structure and function. Finally, once I understand how these systems work, then I will use the results to develop new types of materials based on liquid proteins. For example, I intend to develop new biological sensors for the detection of toxic gases such as carbon monoxide, or active wound dressings that supply oxygen to the wound during healing.