Fundamental Studies on Spider Egg Case Silk Biomaterials and their Mimics

非技术概述丝绸是一种迷人的自然产生的生物材料，对人类文明产生了巨大的影响。尽管蚕丝是被研究最多的生物材料，部分原因是由于其广泛的可获得性，但现有蜘蛛丝的多样性可能导致迄今为止未被探索的新一代生物材料的出现。蜘蛛会产生许多不同形式的丝，包括用来制作蛋壳的丝。与蜘蛛拖丝(通常用作蜘蛛网的脚手架)和蚕丝相比，蜘蛛卵壳丝蛋白和生物聚合物纤维几乎没有被研究过。然而，它的机械性能(即韧性)以及保守和重复的基因序列已被研究并表明与其他蜘蛛丝有显著不同。蜘蛛蛋壳丝和含有纳米颗粒的生物材料复合材料中的分子结构和机械功能关系将允许开发具有可预测的光学、机械和热性能的新的生物非常规材料。这项生物材料研究汇集了生物化学、生物材料和生物工程的各个方面，这需要一个多样化的科学团队，包括来自亚利桑那州立大学(ASU)的物理学家、化学家、生物化学家和生物工程师，以及与阿贡国家实验室(ANL)的合作。这项多机构和多学科的研究将使研究生、本科生和高中生接触到现代跨学科研究以及现代通信和团队合作工具，以建立和维护跨多个实验室和研究所的研究。技术概述蜘蛛产生不同形式的丝蛋白或蜘蛛，其中管状和腺泡状的丝用来构建卵壳。许多蜘蛛蛋壳丝蛋白的力学性质(即韧性)以及保守和重复的基因序列是已知的，并显示出与其他用于制造更多研究较多的牵引式蜘蛛丝的蛋白质显著不同。拟议的研究小组计划探索蜘蛛蛋壳丝、蜘蛛蛋壳丝蛋白主题衍生的蜘蛛丝多肽以及蛋壳丝与纳米颗粒的生物材料纳米复合材料中的结构与功能关系。利用最近开发的获得大量同位素浓缩的蜘蛛卵壳丝绸的方法，将使用先进的磁共振技术研究分子结构和动力学。除了天然的蜘蛛丝，还将在蜘蛛卵壳蛋白重复基序的多肽模拟物上投入大量努力，从而进行结构功能研究、自我组装，并有可能在长期内克服生物生产瓶颈，用于实际应用。利用蜘蛛丝多肽和加工后的蜘蛛蛋壳丝，将针对特定的生物材料应用设计和生成性能可调的纳米颗粒-丝素复合生物材料。蜘蛛丝多肽、它们的模拟物和纳米复合材料的生物相容性将在体外和体内进行全面的研究。这一奖项反映了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 SummarySilk is a fascinating, naturally occurring biomaterial that has had a large impact on human civilization. Although silkworm silk is the most investigated biomaterial, in part because of wide availability, the diversity of spider silks available can lead to new generations of hitherto unexplored biomaterials. Spiders produce many different forms of silk including ones used to construct egg cases. Spider egg case silk proteins and biopolymer fibers have scarcely been studied, compared to spider dragline silk (commonly used to as the scaffolding of spider webs) and silkworm silk. Yet, its mechanical properties (i.e., toughness) and conserved and repetitive gene sequence have been studied and shown to be significantly different from other spider silks. The molecular structure- and mechanical-function relationship in spider egg case silks and biomaterial composites with nanoparticles will allow for the development of new bionanomaterials with predictably tunable optical, mechanical and thermal properties. This biomaterials research brings together aspects of biochemistry, biomaterials and bioengineering, which requires a diverse scientific team, including physicists, chemists, biochemists and bioengineers from Arizona State University (ASU) and collaborations with Argonne National Laboratory (ANL). This multi-institutional and multi-disciplinary research will expose graduate, undergraduate and high school students to modern transdisciplinary research and modern communication and teamwork tools for building and maintaining research across multiple labs and institutes. Technical SummarySpiders produce different forms of silk proteins or spidroins, of which, tubuliform and aciniform silk is used to construct egg cases. The mechanical properties (i.e., toughness) and conserved and repetitive gene sequence are known for many spider’s egg case silk proteins and shown to be significantly different from other proteins used to make the more commonly studied dragline spider silks. The proposed research team plans to explore the structure-function relationship in spider egg case silks, spider silk polypeptides derived from spider egg case silk protein motifs, and biomaterial nanocomposites of egg case silks with nanoparticles. Using recently developed methods for obtaining appreciable quantities of isotopically enriched spider egg case silks, molecular structure and dynamics will be investigated using advanced magnetic resonance techniques. Besides natural spider silks, significant effort will be placed on peptide mimics derived from spider egg case proteins repetitive motifs, allowing structure-function studies, self-assembly and potentially in the long-term overcoming the bioproduction bottleneck for practical application. Using both spider silk polypeptides and processed spider egg case silk, nanoparticle-silk composite biomaterials with tunable properties will be designed and generated for specific biomaterials applications. The biocompatibility of the spider silk polypeptides, their mimics and nanocomposites will be studied comprehensively in vitro and in vivo.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.