Design of Self-Assembling Triple Helices and Molecular Recognition of Collagen

在人体中，胶原蛋白是体内最丰富的蛋白质，几乎存在于每个组织中。胶原蛋白有一系列的功能，从强健骨骼到增强皮肤的力量，再到在免疫力中发挥关键作用。胶原蛋白是由分子组分的多步骤自组装序列构建的。尽管胶原蛋白的无处不在和重要性，潜在的结构，稳定性和组装机制知之甚少。Rice大学的Hartgerink教授进行研究，以确定胶原蛋白的稳定性规律，并探索其组装机制。这一基础知识可以帮助我们更好地理解与胶原蛋白功能障碍相关的疾病，也有助于设计下一代模拟胶原蛋白的生物材料。该研究项目为化学设计与生物学和医学相结合的跨学科本科和研究生教育项目提供了基础。高中科学教师被招募来与Hartgerink团队一起在夏季开发基于前沿研究的令人兴奋的课程，这些课程可以直接转化为他们的高中化学和生物课程。这些老师随后带着他们的整个科学课回来进行演示和实验室参观。将这种跨学科研究与中学教育科学目标相结合，有助于激励学生和教师向STEM相关领域发展。该项目由美国国家科学基金会的大分子、超分子和纳米化学项目资助，主要有两个目标。第一个目标是扩大我们对三螺旋中成对氨基酸相互作用的认识，三螺旋是胶原蛋白自组装的基本单位。这些成对的相互作用调节了三螺旋的稳定性以及它们的自组装。扩大这一知识库有助于我们了解这一重要且极其丰富的蛋白质家族。此外，它还为化学家设计胶原蛋白基材料提供了新的工具，这对各种生物医学应用都很重要。第二个目标是描述一个合理的系统，为胶原蛋白家族的任何成员的特定分子识别。这些胶原靶向肽（ctp）利用上述发现的成对相互作用对给定的胶原蛋白三螺旋进行序列特异性分子识别。ctp在高度复杂的化学环境中发挥作用，比如在一片组织中，数百个其他相互竞争的分子共存。这些ctp的设计应该允许它们专门针对任何天然细胞外基质胶原，先天免疫系统中发现的胶原或细菌和病毒中发现的胶原。

In humans, collagen is the most abundant protein in the body and is found in nearly every tissue. Collagen has a huge array of functions from toughening our bones and giving strength to our skin to playing a key role in immunity. Collagen is constructed by a multistep sequence of self-assembly of the molecular components. Despite collagen's ubiquity and importance, the underlying structure, stability and mechanism of assembly are poorly understood. Prof. Hartgerink of Rice University conducts research to determine the rules of collagen stability and probe the assembly mechanisms. This fundamental knowledge could lead to a better understanding of diseases associated with collagen malfunction and also help with the design of next-generation biomaterials which mimic collagen. This research project provides the basis for interdisciplinary undergraduate and graduate education programs which combine chemical design with biology and medicine. High school science teachers are recruited to work with the Hartgerink group in the summer to develop exciting curriculum based on cutting edge research that can be directly translated to their high school chemistry and biology courses. These teachers later return with their entire science class for demonstrations and laboratory tours. Integration of this interdisciplinary research with secondary education science goals helps to inspire both the students as well as their teachers toward STEM related fields.There are two main goals in this project funded by the Macromolecular, Supramolecular and Nanochemistry Program of the National Science Foundation. The first goal is to expand our knowledge of pairwise amino acid interactions in the triple helix, the fundamental unit of collagen self-assembly. These pairwise interactions modulate the stability of triple helices as well as their self-assembly. Expanding this knowledge base is helping us to understand this important and extremely abundant protein family. In addition, it is providing new tools for chemists to design collagen based materials which are important for a wide variety of biomedical applications. The second goal is to describe a rational system for the specific molecular recognition of any member of the collagen family. These collagen targeting peptides (CTPs) use the pairwise interactions discovered above for sequence specific molecular recognition of a given collagen triple helix. CTPs work in highly complicated chemical environments such as a slice of tissue where hundreds of other competing molecules co-exist. The design of these CTPs should allow them to specifically target any natural extracellular matrix collagens, collagens found in the innate immune system or those found in bacteria and viruses.