Biochimica et Biophysica Acta (BBA) - General Subjects ( IF 3 ) Pub Date : 2021-06-06 , DOI: 10.1016/j.bbagen.2021.129941 A Antosova 1 , M Gancar 1 , Z Bednarikova 1 , J Marek 1 , D Zahn 2 , S Dutz 2 , Z Gazova 1
Background
The surface of nanoparticles (NPs) is an important factor affecting the process of poly/peptides' amyloid aggregation. We have investigated the in vitro effect of trisodium citrate (TC), gum arabic (GA) and citric acid (CA) surface-modified magnetite nanoparticles (COAT-MNPs) on hen egg-white lysozyme (HEWL) amyloid fibrillization and mature HEWL fibrils.
Methods
Dynamic light scattering (DLS) was used to characterize the physico-chemical properties of studied COAT-MNPs and determine the adsorption potential of their surface towards HEWL. The anti-amyloid properties were studied using thioflavin T (ThT) and tryptophan (Trp) intrinsic fluorescence assays, and atomic force microscopy (AFM). The morphology of amyloid aggregates was analyzed using Gwyddion software. The cytotoxicity of COAT-MNPs was determined utilizing Trypan blue (TB) assay.
Results
Agents used for surface modification affect the COAT-MNPs physico-chemical properties and modulate their anti-amyloid potential. The results from ThT and intrinsic fluorescence showed that the inhibitory activities result from the more favorable interactions of COAT-MNPs with early pre-amyloid species, presumably reducing nuclei and oligomers formation necessary for amyloid fibrillization. COAT-MNPs also possess destroying potential, which is presumably caused by the interaction with hydrophobic residues of the fibrils, resulting in the interruption of an interface between β-sheets stabilizing the amyloid fibrils.
Conclusion
COAT-MNPs were able to inhibit HEWL fibrillization and destroy mature fibrils with different efficacy depending on their properties, TC-MNPs being the most potent nanoparticles.
General significance
The study reports findings regarding the general impact of nanoparticles' surface modifications on the amyloid aggregation of proteins.
中文翻译:
表面改性的磁铁矿纳米粒子影响溶菌酶淀粉样蛋白纤维化
背景
纳米颗粒(NPs)的表面是影响多肽类淀粉样蛋白聚集过程的重要因素。我们研究了柠檬酸三钠 (TC)、阿拉伯胶 (GA) 和柠檬酸 (CA) 表面改性磁铁矿纳米粒子 (COAT-MNPs) 对鸡蛋清溶菌酶 (HEWL) 淀粉样蛋白原纤维化和成熟 HEWL 原纤维的体外影响.
方法
动态光散射 (DLS) 用于表征所研究的 COAT-MNP 的物理化学性质,并确定其表面对 HEWL 的吸附潜力。使用硫代黄素 T (ThT) 和色氨酸 (Trp) 内在荧光测定和原子力显微镜 (AFM) 研究抗淀粉样蛋白特性。使用 Gwyddion 软件分析淀粉样蛋白聚集体的形态。使用台盼蓝 (TB) 测定法确定 COAT-MNPs 的细胞毒性。
结果
用于表面改性的试剂会影响 COAT-MNP 的理化特性并调节其抗淀粉样蛋白的潜力。ThT 和内在荧光的结果表明,抑制活性源于 COAT-MNP 与早期淀粉样蛋白前体的更有利的相互作用,可能减少了淀粉样蛋白原纤维化所需的细胞核和低聚物的形成。COAT-MNPs 也具有破坏潜力,这可能是由与原纤维的疏水残基相互作用引起的,导致稳定淀粉样原纤维的 β-折叠之间的界面中断。
结论
COAT-MNPs 能够抑制 HEWL 原纤维化并破坏成熟原纤维,根据其性质不同,TC-MNPs 是最有效的纳米颗粒。
一般意义
该研究报告了有关纳米粒子表面修饰对蛋白质淀粉样蛋白聚集的一般影响的发现。