Utilizing Pairwise Interactions to Understand Collagen Triple Helix Assembly

Simple item page
dc.contributor.advisorHartgerink, Jeffrey D.
dc.contributor.committeeMemberMarti-Arbona, Angel
dc.creatorCole, Carson Calvin
dc.date.accessioned2024-08-30T18:49:29Z
dc.date.created2024-08
dc.date.issued2024-07-30
dc.date.submittedAugust 2024
dc.date.updated2024-08-30T18:49:29Z
dc.descriptionEMBARGO NOTE: This item is embargoed until 2026-08-01
dc.description.abstractCollagen, the most abundant protein in the human body, exhibits diverse physical structures upon assembly. Despite the remarkable similarity in the chemical sequence of amino acids within the collagen triple helix, the origins of the resulting macromolecular properties remain poorly understood in some cases. This thesis investigates collagen supramolecular assembly by synthesizing, characterizing, and applying a range of collagen mimetic peptides to elucidate pairwise interaction geometry, collagen folding, and polymerization. Collagenous proteins have the canonical amino acid sequence of Xaa-Yaa-Gly, where the Xaa is frequently proline and the Yaa is 4-hydroxyproline, respectively. Substitutions of the Xaa and Yaa positions lead to the relative stability of a pairwise interaction in the triple helix. By analyzing the stabilizing and destabilizing effects of pairwise cation-π interaction geometries between cationic and aromatic amino acids in two sequential relationships, axial and lateral, we showed only the axial relationship is stabilizing. By understanding the nuances of amino acid presentation in the triple helix, lateral charge pairs stabilized the triple helix when the cation was in the Xaa position, and the anion was in the Yaa position. As a result, we expanded the design toolbox for collagen mimetic design. Most natural collagens are heterotrimeric, where the three strands are nonequivalent. Incorporating these pairwise interactions yielded an ABC-type heterotrimeric crystal structure with excellent specificity. This specificity enhanced the folding rate of the triple helix, and we confirmed that the folding paradigm was concentration-independent. We further demonstrated that heterotrimeric collagens undergo an equilibrium-mediated assembly process that necessitates complete unfolding before adopting its constituent strands’ correct ABC register. Furthermore, this work incorporated cation-π interactions to develop a hydrogel material emulating fibrous collagens. The peptide structure formed diverse, porous, and fibrous networks upon assembly. In addition, by simple oxidation, we demonstrated that templating the cation-π interaction can introduce intrahelical and inter-helical covalent bonds. Given the critical role of the triple helix as the foundation for the macromolecular properties found in the human body, these findings demonstrate the potential to advance our understanding of collagen folding in disease and create next-generation biomimetic scaffolds.
dc.embargo.lift2026-08-01
dc.embargo.terms2026-08-01
dc.format.mimetypeapplication/pdf
dc.identifier.citationCole, Carson Calvin. Utilizing Pairwise Interactions to Understand Collagen Triple Helix Assembly. (2024). PhD diss., Rice University. https://hdl.handle.net/1911/117847
dc.identifier.urihttps://hdl.handle.net/1911/117847
dc.language.isoeng
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.
dc.subjectCollagen
dc.subjectSelf-Assembly
dc.subjectChemistry
dc.subjectProtein Design
dc.subjectPairwise interactions
dc.subjectcation-pi
dc.subjectSupramolecular chemistry
dc.subjectprotein design
dc.subjectde novo design
dc.titleUtilizing Pairwise Interactions to Understand Collagen Triple Helix Assembly
dc.typeThesis
dc.type.materialText
thesis.degree.departmentChemistry
thesis.degree.disciplineNatural Sciences
thesis.degree.grantorRice University
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy
Files
License bundle
Now showing 1 - 2 of 2
No Thumbnail Available
Name:
PROQUEST_LICENSE.txt
Size:
5.84 KB
Format:
Plain Text
Description:
Download
No Thumbnail Available
Name:
LICENSE.txt
Size:
2.98 KB
Format:
Plain Text
Description:
Download
Collections
Rice University Theses and Dissertations