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，对人类文明产生了巨大的影响。虽然蚕丝是研究最多的生物材料，部分原因是广泛的可用性，但可用的蜘蛛丝的多样性可能导致新一代迄今未开发的生物材料。蜘蛛产生许多不同形式的丝，包括用于建造蛋壳的丝。 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。 然而，其机械性能（即，韧性）和保守和重复的基因序列进行了研究，并显示出显着不同于其他蜘蛛丝。 蜘蛛卵壳丝和具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可调光学、机械和热性能的新生物纳米材料。 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，这需要一个多元化的科学团队，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。 这种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和现代沟通和团队合作工具，以建立和维护跨多个实验室和研究所的研究。 蜘蛛产生不同形式的丝蛋白或蛛丝，其中，管状和腺泡状丝用于构建卵壳。 机械性能（即，韧性）和保守和重复的基因序列是已知的许多蜘蛛的卵壳丝蛋白，并显示出显着不同的其他蛋白质用于使更普遍研究拖丝蜘蛛丝。 拟议的研究小组计划探索蜘蛛卵壳丝的结构-功能关系，蜘蛛丝多肽来源于蜘蛛卵壳丝蛋白基序，以及生物材料纳米复合材料的卵壳丝与纳米颗粒。使用最近开发的方法获得可观的同位素富集蜘蛛卵壳丝，分子结构和动力学将使用先进的磁共振技术进行研究。 除了天然蜘蛛丝之外，还将大力研究来自蜘蛛卵蛋白重复基序的肽模拟物，允许结构-功能研究，自组装，并可能在长期克服生物生产瓶颈以供实际应用。 使用蜘蛛丝多肽和加工的蜘蛛卵壳丝，具有可调性能的纳米颗粒-丝复合生物材料将被设计和产生用于特定的生物材料应用。蜘蛛丝多肽的生物相容性，其模拟物和纳米复合材料将在体外和体内进行全面研究。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

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.