Exploring Interactions of Aptamers with Aβ40 Amyloid Aggregates and Its Application: Detection of Amyloid Aggregates.
Yan ZhengXiuhua GengXiaohai YangShaoyuan LiYaqin LiuXiaofeng LiuQing WangKemin WangRuichen JiaYao XuPublished in: Analytical chemistry (2020)
The exhaustive investigating interactions between recognition probes and amyloid aggregates, especially simultaneous recognition events, are challenging and crucial for the design of biosensing probes and further diagnosis of amyloid diseases. In the present work, the interactions of aptamers (Apts) with β-amyloid (Aβ) aggregates were explored thoroughly by single-molecule force spectroscopy (SMFS). Indeed, it was found that the interaction of aptamer1 (Apt1)-amyloid aggregates was different from that of aptamer2 (Apt2)-Aβ40 aggregates at the single-molecule level. Especially, the interaction force of Apt1-Aβ40 fibril showed a double distinguishing Gaussian fitting. The only unimodal distribution of the force histogram was displayed for the interactions of Apt2-Aβ40 oligomer, Apt2-Aβ40 fibril, and Apt1-Aβ40 oligomer. More intriguingly, two Apts could bind to amyloid aggregates simultaneously. With the assistance of two Apts recognition, a novel sensitive dual Apt-based surface plasmon resonance (SPR) sensor using Au nanoparticles (AuNPs) was developed for quantifying Aβ40 aggregates. The dual Apt-based SPR sensor not only avoided the limitation of steric hindrance and epitope but also employed simple operation as well as inexpensive recognition probes. A detection limit as low as 0.2 pM for Aβ40 oligomer and 0.05 pM for Aβ40 fibril could be achieved. Moreover, the established sensor could be successfully applied to detect Aβ40 aggregates in artificial cerebrospinal fluid (CSF) and undiluted real CSF. This work could provide a strategy to monitor a simultaneous recognition event using SMFS and broaden the application of Apts in the diagnosis of neurodegenerative diseases.
Keyphrases
- single molecule
- living cells
- atomic force microscopy
- cerebrospinal fluid
- label free
- sensitive detection
- particulate matter
- small molecule
- gold nanoparticles
- computed tomography
- high resolution
- risk assessment
- loop mediated isothermal amplification
- water soluble
- nucleic acid
- fluorescent probe
- diffusion weighted
- monoclonal antibody
- solid state