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Title:Quantification of molecular-level events at nanoparticle-biological interfaces
Author(s):Zhang, Xi
Director of Research:Murphy, Catherine J
Doctoral Committee Chair(s):Murphy, Catherine J
Doctoral Committee Member(s):Gewirth, Andrew A; Kraft, Mary L; Pedersen, Joel A
Department / Program:Chemistry
Discipline:Chemistry
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Gold nanoparticles
Lipid corona formation
Cell migration
Surface Chemistry
Nano-bio interfaces
Nano-bio interaction
Abstract:Nanomaterials exhibit various interesting and fundamental properties that are distinctly different from their bulk or molecular scale counterpart. The fascinating size- and shape-dependent optical properties of gold nanoparticles, in particular, along with highly tunable sizes and shapes as well as ease of surface modification, enable a variety of applications. However, many of those applications are developed in controlled environments, making it difficult to predict the biological responses upon exposure of nanomaterials given the complexity of biological systems at the molecular, cellular, tissue and organism levels, and the nanomaterials investigated with a broad range of physiochemical properties. The promises and advancements in nanotechnology increase the likelihood of engineered nanomaterials coming into contact with humans and the environment. The potential for adverse biological and environmental impacts of nanomaterial exposure is considerable and needs to be addressed to ensure the sustainable and biologically acceptable development of nanomaterials. Therefore, a fundamental understanding of how nanoparticles impact and interact with living systems is imperative. A molecular-level insight to the complex nanoparticle-biological interface in order to establish not just correlation but also causality, while challenging, is the key to make more informed decisions and improvements in nanotechnology. The main emphasis of this thesis is to use gold nanoparticles as a platform to probe at the nano-bio interface with analytical techniques to further examine the ways in which nanoparticles exert their effects at the molecular level. In Chapter 1, we introduce the concept of nanomaterials, especially gold nanomaterials, and their unique properties. The syntheses of gold nanoparticles are introduced. The surface modification of gold nanoparticles, including layer-by-layer polyelectrolytes coating and self-assembled monolayers of thiolated molecules, are introduced. We address the importance of probing the nano-bio interfaces and discuss the challenges of applying nanomaterials in biological systems. Formation of a protein corona around nanoparticles when immersed into biological fluids is well-known, but less studied is the formation of lipid coronas around nanoparticles. In chapter 2, we systematically explored the impact of nanoparticle surface chemistry and lipid character on the formation of lipid coronas. 14 nm gold nanoparticles with three different nanoparticle surface chemistries (two cationic, one anionic) were exposed to a series of lipid vesicles of four different compositions. A combination of qualitative and quantitative methods was developed with a “pull-down” scheme to assess the degree of lipid corona formation in these systems. Collective data demonstrate both evidence and quantities of phospholipids in vesicles extracted and bound to cationic gold nanoparticles, indicating a lipid corona formation on both types of cationic gold nanoparticles. Different degrees of binding to both cationic gold nanoparticles were observed in the binary vesicles systems, and different compositions of lipids may lead to different lipid coronas, independent of abundance of lipids. Little lipid corona was formed on anionic gold nanoparticles, supporting the electrostatic nature of the interactions. Variability in nanoparticles and lipid vesicles may significantly influence the results, while insufficient purification of nanoparticle solutions can lead to free ligand, which competes for lipid binding and can give erroneous conclusions about NP-lipid affinities. While the experimental concept of assessing nanoparticle impacts has been focused on the direct interactions of nanoparticles with cells/organisms, more evidence shows that understanding interactions of nanoparticles with microenvironments within cells has the potential to more accurately predict the fate and effects of nanoparticles in living systems. In chapter 3, our principle hypothesis is that the absorption of biomolecules onto gold nanoparticles make it possible to alter signaling chemoattractant gradients in their local microenvironments and thus to influence the cell chemotaxis behavior. µ-Slide chemotaxis assay was employed to characterize and compare the THP-1 cells migration in the gradient of monocyte chemoattractant protein-1 (MCP-1) upon exposure to gold nanoparticles with four different surface chemistries (two anionic, one cationic, one neutral). By time-lapse microscopy, the forward migration indices and p-values by the Rayleigh test, the characteristic parameters for chemotaxis, along with the center of mass, velocity and directionality of the cells, were quantified and statistically analyzed. Anionic poly(sodium 4-styrenesulfonate) coated gold nanoparticles were found to significantly reduce the chemotaxis effect of TPH-1 cells under the described experimental conditions. Free ligands in nanoparticle solutions may also be an important accountable source for altered cell behaviors.
Issue Date:2020-04-22
Type:Thesis
URI:http://hdl.handle.net/2142/108263
Rights Information:Copyright 2020 Xi Zhang
Date Available in IDEALS:2020-08-27
Date Deposited:2020-05


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