Collagen-mimetic peptides for diagnosis and analysis

Collagen, the most abundant protein in the human body, is an essential scaffold for tissue development, regulation, and homeostasis. As a major structural component of the extracellular matrix, collagen is not static. Rather, it is highly diverse and dynamic, actively participating in tissue physiology. Collagen can be a challenging protein to study due to its massive size and heterogeneity across subtypes. A valuable tool to study and better understand collagen is a technology known as collagen-mimetic peptides (CMPs), which are synthetic peptides that mimic the natural structure of collagen. These peptides can be applied to study collagen structure and function, from its macromolecular architecture in tissues to the significance of molecular modifications on its amino acid sidechains. This thesis explores the application of CMPs in diagnostic applications, in which CMPs detect aberrations in native collagen, and analytical contexts, in which CMPs act as a simplified system to understand collagen biochemistry. Chapter 2 investigates the ability of CMPs to identify collagen remodeling in a mouse model of pulmonary fibrosis, demonstrating their potential as non-invasive diagnostic tools for fibrotic diseases. Chapter 3 analyzes the collagen-rich desmoplastic reaction surrounding PDAC in murine models and human samples, highlighting the utility of CMPs in characterizing tumor microenvironments. Finally, Chapter 4 examines the structural implications of threonine phosphorylation on collagen stability, showcasing the value of CMPs in studying posttranslational modifications. The findings discussed in this thesis lay a foundation for future CMP applications in targeted drug delivery and biomaterials design.

Name thesis:degree_name

Doctoral

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Chemistry

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2024

Author dc:creator

• Borgula, Isabella M.

Advisor dc:contributor.advisor

• Raines, Ronald T.

Statement dc:rights

• Attribution-ShareAlike 4.0 International (CC BY-SA 4.0)
• Copyright retained by author(s)

Licence dc:rights.uri

• https://creativecommons.org/licenses/by-sa/4.0/

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/157566

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/157566