Designing and Understanding High-performance Titin Polymers Using Synthetic Biology

非技术描述：合成生物学提供了一条从可再生原料(如生物质衍生的糖)通过环境友好型工艺生产材料的新途径。此外，合成生物学可以更精确地控制材料的特性。该项目将使用合成生物学来生产、表征和了解一种新型的基于蛋白质的纤维材料，称为Titin聚合物，这种材料将使用工程菌从可再生的原料中生产。该项目将提供目前未知的关于Titin聚合物中序列-性质关系的细节，以指导未来高性能生物材料的设计。该项目还将从不同的蛋白质和生物体来源中创造多种新型聚合物，这些聚合物可能具有出色的机械性能。此外，该项目将作为一个关键的概念验证，使用合成生物学不仅生产生物材料，而且了解生物材料的分子机制。提出的合成生物学策略可以用于研究许多其他类型的材料。该项目还将通过创造新的高性能生物材料来造福社会，这种材料可能会取代石油原料制成的合成纤维，从而减少二氧化碳排放和保护环境。技术描述：该项目的目标是使用这种合成生物学策略来设计、合成、表征和分析一种新型的超高相对分子质量(UHMW)Titin聚合物，以了解蛋白质序列与材料机械性能之间的关系。该项目将使用合成生物学的方法来合成一系列具有不同但精确控制的单体(即免疫球蛋白(Ig)结构域)组成和顺序以及在Ig结构域的表面或核心残基上具有突变的UHMW titin聚合物。这些不同的UHMW Titin聚合物将被纺制成纤维，并对纤维的力学性能进行表征。通过分析由不同TiTiN聚合物制成的纤维的机械性能，该项目将揭示导致TiTiN纤维具有高拉伸强度、韧性和阻尼能的序列-性能关系。具体目标包括(1)了解免疫球蛋白-免疫球蛋白相互作用对纤维强度和韧性的影响，(2)了解免疫球蛋白折叠能对纤维阻尼能的影响，以及(3)从基因组数据库中探索新型聚合物的免疫球蛋白结构域。从该项目学到的知识将转化为设计规则，以指导未来设计具有可预测性能的微生物生产的高性能TiTiN纤维，适用于广泛的应用。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Non-technical description:Synthetic biology offers a new route of material production from renewable feedstock (such as biomass-derived sugars) through environmentally-friendly processes. Furthermore, synthetic biology enables more precise control over material properties. This project will use synthetic biology to produce, characterize, and understand a new type of protein-based fiber material, called titin polymers, that will be produced from renewable feedstock using engineered bacteria. This project will provide currently unknown details about sequence-property relationships in titin polymers that can guide design of future high-performance biomaterials. This project will also create multiple novel polymers from diverse protein and organism sources that may have outstanding mechanical properties. Additionally, this project will serve as a critical proof-of-concept for using synthetic biology to not only produce biomaterials but also understand the molecular mechanisms of biomaterials. The proposed synthetic biology strategy can be used to study many other types of materials. This project will also benefit society by creating new high-performance biomaterials that can potentially replace synthetic fibers made from petroleum feedstock, thus reducing CO2 emission and protecting the environments.Technical description:The goal of this project is to use this synthetic biology strategy to design, synthesize, characterize, and analyze a new type of ultra-high molecular weight (UHMW) titin polymers to understand the relationship between protein sequences and material mechanical properties. This project will use synthetic biology approaches to synthesize a series of UHMW titin polymers with different but precisely controlled monomer (i.e., immunoglobulin (Ig) domain) compositions and orders and with mutations on either the surface or core residues of the Ig domains. These different UHMW titin polymers will be spun into fibers, and fiber mechanical properties will be characterized. By analyzing the mechanical properties of fibers made from different titin polymers, this project will uncover the sequence-property relationships that give rise to the high tensile strength, toughness, and damping energy of the titin fibers. Specific aims include (1) understanding the effect of Ig-Ig interactions on fiber strength and toughness, (2) understanding the effect of Ig folding energy on fiber damping energy, and (3) exploring diverse Ig domains from genome database for novel polymers. Knowledge learned from this project will translate into design rules to guide future engineering of microbially-produced high-performance titin fibers with predictable properties for a broad range of applications.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.