Functional Biomolecular Liquids

功能生物分子液体

• 批准号: EP/K026720/1
• 负责人: Adam Perriman
• 金额: $ 101.51万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FK026720%2F1
• 关键词: Functional; Biomolecular; Liquids

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.

设计具有小规模(纳米)结构并结合多种成分的新材料有望导致传感、电子、催化和医学领域的新技术的发展。这些材料可能很难合成，一种新的方法是使用被称为蛋白质的大生物分子作为活性成分。蛋白质是由长链氨基酸组成的，这些氨基酸自身折叠形成复杂的3D结构。在人体内，蛋白质执行各种各样的任务(或功能)，从结合肌肉中的氧气(由蛋白质肌红蛋白执行)，到储存血液中的铁(铁蛋白)，如果这些特性能被转移到合成材料上将是有利的。蛋白质最常见的形式是分散在水溶液中或干粉中，有趣的是，直到最近，纯液相中的蛋白质还不存在，即加热干燥的蛋白粉不会导致其融化。从本质上说，这意味着有一个尚未发现的生物物质的缺失阶段。由于蛋白质分子的分子尺寸相对较大(纳米级)，没有纯的液体蛋白质相，这是一个有趣的现象，在纳米颗粒中也可以看到。之所以会出现这种情况，是因为物质的液态受到分子间引力的稳定，分子间力的作用距离比单个分子的大小大得多。然而，蛋白质的情况并非如此，因为与它们之间的作用力范围相比，它们的结构很大。本质上，蛋白质分子在固相中被牢牢地结合在一起，加热不会使它们融化，相反，会破坏它们的分子结构，导致分解。我研究的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访问缺失的蛋白质液相。为了做到这一点，我将人工(合成)聚合物表面活性剂分子连接到蛋白质的表面，以产生具有长卷须的蛋白质分子，这些分子可以与其他蛋白质分子进行更远距离的相互作用。这些聚合物表面活性剂分子带负电荷，并且只附着在蛋白质表面的带正电荷的基团上。因此，有必要首先对蛋白质分子的表面进行化学改变，使其更带正电荷，这样就可以连接足够多的聚合物表面活性剂分子。在我的初步研究中，我使用这种方法生产了铁蛋白和肌红蛋白的液体，这些液体不含水，在室温附近融化。真正令人震惊的是，尽管蛋白质分子已经进化到在水环境中工作，但它们在纯液体中的结构似乎没有改变，就肌红蛋白而言，蛋白质仍然可以结合氧气。我提议的工作使我能够应用我在生物化学、材料科学和物理化学方面的知识来开发一种新的杂化生物液体，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。在每一种情况下，我都将研究液体的分子结构，以及它们的组成和性质，如粘度，我还将测试蛋白质的功能。这不仅将提供一系列新的活性液体，还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，我将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来检测有毒气体，如一氧化碳，或在愈合过程中为伤口提供氧气的活性伤口敷料。

项目成果

Electrospun Cellulose-Silk Composite Nanofibres Direct Mesenchymal Stem Cell Chondrogenesis in the Absence of Biological Stimulation

电纺纤维素-丝复合纳米纤维在没有生物刺激的情况下直接间充质干细胞软骨形成

• DOI: 10.1101/434316
• 发表时间: 2018
• 作者: Begum R

Artificial membrane-binding proteins stimulate oxygenation of stem cells during engineering of large cartilage tissue.

• DOI: 10.1038/ncomms8405
• 发表时间: 2015-06-17
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Armstrong JPK;Shakur R;Horne JP;Dickinson SC;Armstrong CT;Lau K;Kadiwala J;Lowe R;Seddon A;Mann S;Anderson JLR;Perriman AW;Hollander AP
• 通讯作者: Hollander AP

Engineering Anisotropic Muscle Tissue using Acoustic Cell Patterning.

• DOI: 10.1002/adma.201802649
• 发表时间: 2018-10
• 期刊: Advanced materials (Deerfield Beach, Fla.)
• 作者: Armstrong JPK;Puetzer JL;Serio A;Guex AG;Kapnisi M;Breant A;Zong Y;Assal V;Skaalure SC;King O;Murty T;Meinert C;Franklin AC;Bassindale PG;Nichols MK;Terracciano CM;Hutmacher DW;Drinkwater BW;Klein TJ;Perriman AW;Stevens MM
• 通讯作者: Stevens MM

Cell paintballing using optically targeted coacervate microdroplets.

• DOI: 10.1039/c5sc02266e
• 发表时间: 2015-11-01
• 期刊: Chemical science
• 影响因子: 8.4
• 作者: Armstrong JPK;Olof SN;Jakimowicz MD;Hollander AP;Mann S;Davis SA;Miles MJ;Patil AJ;Perriman AW
• 通讯作者: Perriman AW

Mechanics and band gaps in hierarchical auxetic rectangular perforated composite metamaterials

• DOI: 10.1016/j.compstruct.2016.10.121
• 发表时间: 2017-01-15
• 期刊: COMPOSITE STRUCTURES
• 影响因子: 6.3
• 作者: Billon, Kevin;Zampetakis, Ioannis;Hetherington, Alistair
• 通讯作者: Hetherington, Alistair