Interaction of Colloidal Gold Nanoparticles with Model Serum Proteins: The Nanoparticle-Protein ‘Corona’ from a Physico-Chemical Viewpoint

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dc.contributor.advisorLink, Stephanen_US
dc.contributor.committeeMemberMarti, Angelen_US
dc.contributor.committeeMemberDrezek, Rebekahen_US
dc.creatorDominguez-Medina, Sergioen_US
dc.date.accessioned2016-01-14T22:13:08Zen_US
dc.date.available2016-01-14T22:13:08Zen_US
dc.date.created2015-12en_US
dc.date.issued2015-09-15en_US
dc.date.submittedDecember 2015en_US
dc.date.updated2016-01-14T22:13:09Zen_US
dc.description.abstractWhen nanoparticles come in contact with biological fluids they become coated with a mixture of proteins present in the media, forming what is known as the nanoparticle-protein ‘corona’. This corona changes the nanoparticles’ original surface properties and plays a central role in how these get screened by cellular receptors. In the context of biomedical research, this presents a bottleneck for the transition of nanoparticles from research laboratories to clinical settings. It is therefore fundamental to probe these nanoparticle-protein interactions in order to understand the different physico-chemical mechanisms involved. This thesis is aimed to investigate the exposure of colloidal gold nanoparticles to model serum proteins, particularly serum albumin, the main transporter of molecular compounds in the bloodstream of mammals. A set of experimental tools based on optical microscopy and spectroscopy were developed in order to probe these interactions in situ. First, the intrinsic photoluminescence and elastic scattering of individual gold nanoparticles were investigated in order to understand its physical origin. These optical signals were then used to measure the size of the nanoparticles while in Brownian diffusion using fluctuation correlation spectroscopy. This spectroscopic tool was then applied to detect the binding of serum albumin onto the nanoparticle surface, increasing its hydrodynamic size. By performing a binding isotherm as a function of protein concentration, it was determined that serum albumin follows an anti-cooperative binding mechanism on negatively charged gold nanoparticles. This protein monolayer substantially enhanced the stability of the colloid, preventing their aggregation in saline solutions with ionic strength higher than biological media. Cationic gold nanoparticles in contrast, aggregated when serum albumin was present at a low protein-to-nanoparticle ratio, but prevented aggregation if exposed in excess. Single-molecule fluorescence microscopy revealed that under low protein-to-nanoparticle binding ratios, serum albumin irreversibly unfolds upon adsorption and spreads across the available nanoparticle surface area. Unfolded proteins then interact with one another, triggering nanoparticle aggregation. Fibrinogen and globulin also triggered aggregation when exposed to cationic nanoparticles. In an effort to relate these physico-chemical observations to relevant biological parameters, the uptake of protein coated gold nanoparticles by a model cancer cell line was investigated under different incubation conditions. Those nanoparticles pre-incubated with bovine serum albumin before fetal bovine serum were found to be uptaken three times more than those only incubated in serum.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationDominguez-Medina, Sergio. "Interaction of Colloidal Gold Nanoparticles with Model Serum Proteins: The Nanoparticle-Protein ‘Corona’ from a Physico-Chemical Viewpoint." (2015) Diss., Rice University. <a href="https://hdl.handle.net/1911/87834">https://hdl.handle.net/1911/87834</a>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/87834en_US
dc.language.isoengen_US
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.subjectNanoparticlesen_US
dc.subjectProteinsen_US
dc.titleInteraction of Colloidal Gold Nanoparticles with Model Serum Proteins: The Nanoparticle-Protein ‘Corona’ from a Physico-Chemical Viewpointen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentChemistryen_US
thesis.degree.disciplineNatural Sciencesen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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