MOLECULAR PACKING AND ORIENTATION OF SELF-ASSEMBLED PEPTIDE AMPHIPHILE SYSTEMS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 自组装纳米结构已被成功地用于医学、材料科学和工程中的各种目的。这项拟议的研究集中在一种特殊的自组装分子上，这种分子被称为多肽两亲分子，它形成了由纳米纤维组成的分子水凝胶。这些分子已经被西北大学的实验室用来实现一系列生物工程目标：作为细胞和组织人工支架；作为引导干细胞分化、细胞迁移、细胞反应和损伤后组织再生的生物材料；以及作为细胞、肽、核酸和蛋白质输送的载体。我们的实验重点是了解这些分子通过研究纳米纤维材料中的分子取向和空间分布而创建的超分子结构。总体目标是验证特定的热力学、动力学和分子动力学自结合模型，并揭示这些工程生物材料的结构-功能关系。未来生物医学和治疗学对这些特定分子的工程设计取决于对这些水凝胶系统组织行为的所有水平的了解。我们相信，X射线衍射是对我们目前的表征方法的一个有价值的补充，因为它允许对这种非晶态体系进行分子水平的分辨。特别是，与其他传统的聚合物表征方法相比，同步辐射X射线源的使用将提供最高水平的分子堆积分辨率。与目前在理解其他基于肽/蛋白质的自组装系统方面取得重大进展的光纤衍射学家的合作，将导致技术、结果的有效转化，并在这两个领域对社会产生更广泛的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Self-assembled nanostructures have been successfully exploited for a variety of purposes in medicine, materials science, and engineering. The proposed research centers on a particular kind of self-assembling molecule called peptide amphiphiles that form molecular hydrogels composed of nanofibers. These molecules have been utilized by our laboratory at Northwestern University to achieve a collection of bioengineering goals: as cell and tissue artificial scaffolds; as biomaterials that direct stem cell differentiation, cell migration, cellular response, and tissue regeneration after injury; and as vehicles for cell, peptide, nucleic acid, and protein delivery. Our experiments center on understanding supramolecular structures these molecules create by investigating molecular orientations and spatial distributions within the nanofiberous materials. The overall goal is to validate specific thermodynamic, kinetic, and molecular dynamic models of self-association and to uncover structure-function relationships of these engineered biomaterials. Future engineering of these specific molecules for biomedicine and therapeutics is contingent upon understanding all levels of the organizational behavior of these hydrogel systems. We believe that X-ray diffraction is an valuable addition to our present characterization methodologies by allowing molecular level resolution of this non-crystalline system. In particular, the use of synchrotron X-ray sources will provide the highest level of resolution of molecular packing in contrast to other traditional polymer characterization methodologies. Collaboration with fiber diffractionists currently making great strides in understanding other peptide/protein-based self-assembling systems will lead to effective translation of techniques, results, and broader impact to society across both fields.