Fundamental Studies on Spider Egg Case Silk Biomaterials and their Mimics

丝绸是一种迷人的天然生物材料，对人类文明产生了重大影响。虽然蚕丝是研究最多的生物材料，部分原因是其广泛可用性，但可用的蜘蛛丝的多样性可以导致新一代迄今尚未开发的生物材料。蜘蛛能产生多种不同形式的丝，包括用来制造卵壳的丝。与蜘蛛拖丝（通常用作蜘蛛网的支架）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，它的力学性能（即韧性）和保守和重复的基因序列已被研究，并显示出与其他蜘蛛丝有显著不同。蜘蛛卵丝和纳米颗粒生物材料复合材料的分子结构和机械功能关系将有助于开发具有可预测的光学、机械和热性能的新型生物材料。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，并与阿贡国家实验室（ANL）合作。这项多机构、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、现代沟通和团队合作工具，以便在多个实验室和研究所之间建立和维持研究。蜘蛛产生不同形式的丝蛋白或蛛丝，其中管状和腺状丝用于构建卵壳。许多蜘蛛卵壳丝蛋白的机械性能（即韧性）和保守的重复基因序列是已知的，并被证明与用于制造更常见的拖丝蜘蛛丝的其他蛋白质有显著不同。本课题组计划探索蜘蛛卵丝的结构-功能关系，从蜘蛛卵丝蛋白基序中提取的蜘蛛丝多肽，以及含有纳米颗粒的蜘蛛卵丝生物材料纳米复合材料。利用最近开发的方法获得大量同位素富集的蜘蛛卵卵丝，将利用先进的磁共振技术研究分子结构和动力学。除天然蜘蛛丝外，还将重点研究从蜘蛛卵壳蛋白重复基序中提取的肽模拟物，从而进行结构-功能研究、自组装，并有可能在长期内克服实际应用的生物生产瓶颈。利用蜘蛛丝多肽和加工过的蜘蛛卵丝，纳米颗粒-丝复合生物材料将被设计和生产出具有可调性能的特定生物材料。研究蛛丝多肽及其模拟物和纳米复合材料的体内体外生物相容性。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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.