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

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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.