Engineering Biomaterial - Protein Corona Interactions to Mediate Biological Responses
Author(s)
Pustulka, Samantha M.
Advisor(s)
Champion, Julie
Editor(s)
Collections
Supplementary to:
Permanent Link
Abstract
When biomaterials are introduced into a physiological environment, proteins found within the surrounding biological fluid will rapidly adsorb onto the biomaterial’s surface. This adsorption event creates a layer of protein that governs cell interactions and the immune response to the biomaterial. Proteomics was used for the first time to profile the protein’s adsorbed on the surface of desolvated protein nanoparticles and nanotextured stainless steel surfaces. Gel electrophoresis revealed an increase in the amount of plasminogen adsorbed onto polystyrene nanoparticles upon exposure to increasing hydrodynamic forces. Additionally, fluorescence spectroscopy and circular dichroism measured a change in plasminogen conformation caused by these same hydrodynamic forces, which contributed to the increase in protein adsorption. Bovine serum albumin protein nanoparticles were developed as a carrier and an anti-inflammatory protein therapeutic, AvrA, was incorporated into the nanoparticles. These therapeutic protein nanoparticles were used to increase the migration of inflamed fibroblasts using a scratch assay. A covalently attached ACE2 receptor binding domain protein coating, developed from the SARS-CoV-2 spike glycoprotein, was engineered and used to target ACE2 receptors on endothelial cells. It was proposed that this protein coating can be further developed to treat hyper-inflammation of the endothelium or as a diagnostic to measure antibody titers in convalescent sera. This work demonstrates the importance of characterizing the adsorbed protein layer on biomaterial surfaces to enable rational design of biomaterials based on their surface properties.
Sponsor
Date
2021-05-03
Extent
Resource Type
Text
Resource Subtype
Dissertation