Year of Publication

2015

Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation

College

Arts and Sciences

Department

Chemistry

First Advisor

Dr. Jason DeRouchey

Abstract

With the rapid growth of nanotechnology, situations where nanomaterials will interact with biological systems will unquestionably grow. Therefore, it is increasingly understood that interactions between nanomaterials and biological environments will play an essential role in nanomedicine. Biological polymer networks, including mucus and the extracellular matrix, serve as a filter for the exchange of molecules and nanoparticles. Such polymer networks are complex and heterogeneous hydrogel environments that regulate transport processes through finely tuned particle-network interactions. In chapters 3 and 4, we investigate the role of electrostatics on the basic mechanisms governing the diffusion of charged molecules inside model polymer networks by using fluorescence correlation spectroscopy (FCS). In chapter 3, we show that particle transport of charged probe molecules in charged hydrogels is highly asymmetric and that the filtering capability of the gel is sensitive to the solution ionic strength. Brownian dynamics simulations are in quantitative agreement with our experimental result. In chapter 4, we focus on hyperbranched cationic dendrimer macromolecules (polyamidoamine, PAMAM) which differ from probes in size, charge density and chain flexibilities. Our results show PAMAM has strongly reduced mobility in like charge gels and greatly enhanced apparent diffusivity in oppositely charged gels. Further studies with salt suggest that the oppositely charged polymer network acts as a giant counterion enhancing the mobility of PAMAM by changing its conformation to a more compacted state.

Due to their large surface areas, nanomaterials in biological fluids are modified by adsorption of biomolecules, mainly proteins, to form so called “protein coronas”. These coronas ultimately define the biological identity of the nanoparticles and dictate the interactions of cells with the protein-NP complex. We have studied the adsorption of human transferrin and bovine serum albumin on the surface of sulfonated polystyrene nanoparticle. In chapter 5, we show the formation of multi-layered protein coronas and compare to established adsorption models. In addition we followed for the first time the protein binding kinetics as a function of pH and salt. Through these studies, we aim to gain quantitative knowledge of the dynamic rearrangement of proteins on engineered nanomaterials.

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