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Application and characterization of polymer-protein and polymer-membrane interactions

Burridge, Kevin Michael

Abstract Details

2021, Doctor of Philosophy, Miami University, Chemistry and Biochemistry.
This work is designed to understand how to efficiently synthesize polymers for and to understand two major biotechnology applications - protein-polymer conjugates, and macromolecular surfactants for favorable cell membrane interactions. Polymers are a ubiquitous class of molecules in the world due to the unique and complex properties that arise from combining simple building blocks in particular combinations. Nature has adopted proteins, amino acid polymers that fulfill myriad critical functions. In recent years, the biotechnology industry has begun to manipulate proteins by attaching synthetic polymers to them, conferring invisibility to the immune system for protein drugs, or enhanced stability, activity, or recyclability to enzymes for biocatalysis. A protein molecule on its own is sufficiently complex to require years-long research projects to fully understand. Thus, protein-polymer conjugates are still poorly understood. In this work, we present a technique for the study of conjugates, enabled by reversible deactivation radical polymerization, which by nuclear magnetic resonance allows for an atomic-level view. We also explored the challenge of attaching two distinct polymers to a single protein molecule in an efficient and well-defined manner, which would enable still more complex conjugates. Lipid membranes and the proteins that reside within them are another area of biotechnology that polymers have broken into. Cell membranes and the proteins within them experience a complex play of intermolecular forces. The unique location of membrane proteins makes them difficult to study, as they are not readily crystallized, and resuspension using traditional detergents can be detrimental to protein structure. Styrene-maleic acid copolymers and their relatives are known to form a belt containing lipids and membrane proteins in disk-shaped nanoparticles. These maintain the bilayer shape and avoid the use of detergents and have enabled characterization of previously inaccessible proteins. This work contributed to the area of lipid nanoparticles by designing facile protocols to access macromolecular surfactants on a large scale which overcome the limitations of styrene-maleic acid. In addition, the membrane-disrupting ability of these surfactants allowed for them to act as a component of potentially self-disinfecting materials which could disrupt viral envelopes they contact, mitigating the spread of disease through fomites and air filtration systems.
Dominik Konkolewicz, PhD (Advisor)
Richard Page, PhD (Advisor)
Richard Taylor, PhD (Committee Chair)
Carole Dabney-Smith, PhD (Committee Member)
Jason Berberich, PhD (Committee Member)

Recommended Citations

Citations

  • Burridge, K. M. (2021). Application and characterization of polymer-protein and polymer-membrane interactions [Doctoral dissertation, Miami University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=miami1624882451668094

    APA Style (7th edition)

  • Burridge, Kevin. Application and characterization of polymer-protein and polymer-membrane interactions. 2021. Miami University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=miami1624882451668094.

    MLA Style (8th edition)

  • Burridge, Kevin. "Application and characterization of polymer-protein and polymer-membrane interactions." Doctoral dissertation, Miami University, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=miami1624882451668094

    Chicago Manual of Style (17th edition)