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Curvature Effects on the Adsorption of Plasma Proteins to Polystyrene.

机译:曲率对血浆蛋白吸附聚苯乙烯的影响。

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摘要

The interaction of human serum proteins with nanoparticles is of concern due to the increasing exposure of humans to applications that involve nanomaterials that can ultimately enter the bloodstream. The inclusion of these highly curved surfaces in medical devices, drug delivery technology, diagnostic testing methods, and particles found in air pollution has increased the desire to understand the corresponding adsorption behavior of proteins.;The adsorption behavior of human serum albumin (HSA) was studied using various techniques to measure protein adsorption isotherms for polystyrene films and particles. The particles have curvature approaching the length-scale of protein molecules. Quartz crystal microgravimetry with dissipation monitoring (QCM/D) and dual polarization interferometry (DPI) were analytical tools used to measure the amount of mass adsorbed to the surface of polystyrene films. A solution depletion method was used to measure changes in concentration of bulk protein after exposure to polystyrene nanoparticles; this quantification was carried out using capillary electrophoresis. Several adsorption isotherm models were fit to the data to determine trends in key adsorption parameters as a function of curvature.;The model fits suggest that an increase in surface curvature results in a decrease in protein-protein interactions and adsorption affinity. The decrease in adsorption affinity is well supported in the literature for various proteins interacting with nanoparticles and nanotubes. The decrease in protein-protein interactions was measured by a dye-binding fluorescence assay for intermolecular beta-sheet and supported this finding. Structural changes upon adsorption on less curved surfaces were greater than on more curved surfaces and this result is also supported in the literature.;Protein exchangeability was studied by exposing polystyrene nanoparticles to a mixture of human serum albumin and immunoglobulin G (IgG), the first two proteins in the plasma protein Vroman effect. The amount of HSA and IgG adsorbed to the particles suggest that multi-layer adsorption of HSA occurred and that HSA exchangeability on more curved surfaces increased.
机译:由于人类越来越多地接触涉及最终可能进入血液的纳米材料的应用,因此人类血清蛋白与纳米颗粒之间的相互作用受到关注。将这些高度弯曲的表面包含在医疗设备,药物输送技术,诊断测试方法以及空气污染中发现的颗粒后,人们对了解蛋白质相应吸附行为的需求增加了。人血清白蛋白(HSA)的吸附行为为研究人员使用各种技术测量了聚苯乙烯薄膜和颗粒的蛋白质吸附等温线。颗粒的曲率接近蛋白质分子的长度尺度。具有耗散监测功能的石英晶体微重力法(QCM / D)和双极化干涉法(DPI)是用于测量吸附到聚苯乙烯薄膜表面的质量量的分析工具。使用溶液消耗法测量暴露于聚苯乙烯纳米粒子后大块蛋白质浓度的变化;该定量使用毛细管电泳进行。几种吸附等温线模型都适合于该数据,以确定关键吸附参数随曲率的变化趋势。模型拟合表明表面曲率的增加导致蛋白质-蛋白质相互作用和吸附亲和力的降低。对于与纳米粒子和纳米管相互作用的各种蛋白质,文献中充分支持了吸附亲和力的降低。通过分子间β-折叠的染料结合荧光测定法测量了蛋白质-蛋白质相互作用的降低,并支持了这一发现。在较少弯曲的表面上吸附时的结构变化大于在较大弯曲的表面上的结构变化,这一结果在文献中也得到支持。两种蛋白质在血浆蛋白质中具有弗罗曼效应。吸附到颗粒上的HSA和IgG的量表明发生了HSA的多层吸附,并且在更多曲面上的HSA交换性增加了。

著录项

  • 作者

    Hum, William.;

  • 作者单位

    Carnegie Mellon University.;

  • 授予单位 Carnegie Mellon University.;
  • 学科 Engineering Biomedical.;Biophysics General.
  • 学位 Ph.D.
  • 年度 2011
  • 页码 168 p.
  • 总页数 168
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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