The building blocks of life are proteins. These incredible nanostructures are responsible for forming the diverse infrastructure of living systems and for performing countless biological functions. In Nature, these materials and systems achieve structural complexity and function through highly regulated and controlled assembly of protein building blocks, driven by specific interactions encoded between protein surfaces (protein-protein interactions; PPIs). Despite their significance in Nature, the realization of synthetic protein materials displaying similar structural complexity and functions, remains challenging due to the difficulties in controlling the association and assembly pathways of proteins by design. While some methods have been established to reliably control the association of proteins, the knowledge for instructing and guiding the assembly of protein building blocks down a specific pathway has yet to be created. Here, we investigate how the programmability and high-information content of DNA interactions can be used to program the assembly pathways of proteins to realize novel protein-based materials. Chapter two describes how protein sequence and secondary structure can be manipulated to tune the energy barriers associated with protein association to direct polymerization along specific pathways. Chapter three explores how protein amino acid sequences can be designed to encode multiple, orthogonal DNA interactions onto protein surfaces to drive the assembly of multi-component systems into extended three-dimensional architectures. Chapter four combines both protein and DNA sequence design to encode directional interactions onto protein surfaces with designed interaction strengths that enable proteins to traverse hierarchical assembly pathways, akin to those observed in Nature. Chapter 5 provides a summary of the key conclusions and lessons established through this research as well as an overview of important future directions. Collectively these chapters establish new methods to design and engineer the assembly pathways of proteins which will enable the synthesis and discovery of synthetic protein-based materials with the structural complexity and functions observed in Nature and beyond.

Creator

• Hayes, Oliver George

DOI

• https://doi.org/10.21985/n2-152a-b453

Subject

• Nanotechnology
• Chemistry

Language

• en

Alternate Identifier

• etdadmin_upload_835884
• http://dissertations.umi.com/northwestern:15660

Keyword

• Hierarchical
• Supramolecular
• Proteins
• Self-assembly

Date created

• 2021-01-01

Resource type

• Dissertation

Rights statement

• In Copyright