Title:
Ion-specific and water-mediated effects on protein physical stability

dc.contributor.advisor Behrens, Sven H.
dc.contributor.advisor Bommarius, Andreas S.
dc.contributor.advisor Chernoff, Yury O.
dc.contributor.author Rubin, Jonathan en_US
dc.contributor.committeeMember Chernoff, Yury
dc.contributor.committeeMember Breedveld, Victor
dc.contributor.committeeMember Hud, Nicholas
dc.contributor.department Chemical and Biomolecular Engineering en_US
dc.date.accessioned 2013-06-15T02:43:18Z
dc.date.available 2013-06-15T02:43:18Z
dc.date.issued 2013-03-20 en_US
dc.description.abstract Protein aggregation and physical stability are perpetual concerns in medicine and industry. Misfolded protein can form ordered protein aggregates, amyloids, which are associated with a host of neurodegenerative diseases in mammals and control heritable traits in fungi and yeast. Industrially, amorphous aggregates reduce the efficacy of protein-based therapeutics and activity of enzymes during production and storage. This work studies ion-specific and solvent-based effects on protein physical stability. We show that ion-specificity significantly affects amyloid formation kinetics, aggregate morphology, thermostability, frangibility, and, most intriguingly, prion infectivity in vivo. Forming amyloid in chaotropic or kosmotropic solutions generates predominately weak or strong prion variants, respectively. Ion-specific effects also influenced amorphous aggregation of model proteins and antibodies. To quantify protein - protein stability/affinity, we developed a rapid and reliable diffusion-based technique. Our technique was able to resolve relative differences in colloidal stability between various saline and saccharide solutions. In all, this dissertation expands our understanding of ion-specific and water-mediated interactions with prion proteins and protein dispersions. en_US
dc.description.degree PhD en_US
dc.identifier.uri http://hdl.handle.net/1853/47587
dc.publisher Georgia Institute of Technology en_US
dc.subject Thermostability en_US
dc.subject Antibody formulation en_US
dc.subject Prions en_US
dc.subject Prion strains en_US
dc.subject Protein aggregation en_US
dc.subject Hofmeister effects en_US
dc.subject Dynamic light scattering en_US
dc.subject.lcsh Protein folding
dc.subject.lcsh Proteins
dc.subject.lcsh Proteins Stability
dc.title Ion-specific and water-mediated effects on protein physical stability en_US
dc.type Text
dc.type.genre Dissertation
dspace.entity.type Publication
local.contributor.advisor Chernoff, Yury O.
local.contributor.advisor Bommarius, Andreas S.
local.contributor.corporatename School of Chemical and Biomolecular Engineering
local.contributor.corporatename College of Engineering
relation.isAdvisorOfPublication d9f3d192-f4c7-4db2-ace4-2baadbeb98b6
relation.isAdvisorOfPublication faf2f937-2845-4a43-af4c-3d34a45ece32
relation.isOrgUnitOfPublication 6cfa2dc6-c5bf-4f6b-99a2-57105d8f7a6f
relation.isOrgUnitOfPublication 7c022d60-21d5-497c-b552-95e489a06569
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
jonathan_rubin_201305_phd.pdf
Size:
6.71 MB
Format:
Adobe Portable Document Format
Description: