Real‐Time Observation for Dynamic Oscillation during Self‐Assembly and Clearance of Aβ42

Abstract

AbstractThe dynamic oscillation implicated in structural heterogeneity during the self‐assembly of amyloid peptide 1–42 (Aβ42) may play a crucial role in eliciting cellular responses. We developed a real‐time monitoring platform to observe an oscillatory non‐equilibrium interaction that dominated the Aβ42 clearance by neuronal cells during interplay with an oscillator (lipopolysaccharide, LPS). Molecular dynamics studies indicated that the electrostatic and hydrophobic segments of LPS involved in the temporary heteromolecular association and slightly decelerated the intrinsic thermally–induced protein dynamics of Aβ42. A bait‐specific intervention strategy could temporarily slow down the self‐propagation of Aβ42 to extend the lifetime of autonomous oscillation and augment Aβ42 clearance of neuronal cells. The lifetime increment of oscillation shows a bait concentration‐dependent manner to reflect the non‐equilibrium binding strength. This relationship may serve as a predictor for Alzheimer's disease drug discovery.