A Cantilever‐based Biosensor for Real‐time Monitoring of Interactions between Amyloid‐β(1–40) and Membranes Comprised of Phosphatidylcholine Lipids with Different Hydrophobic Acyl Chains

Abstract

AbstractAccumulating evidence suggests that interaction between amyloid‐β (Aβ) and cell membrane is crucial to the pathogenesis of Alzheimer's disease (AD), and thus an increasing understanding of the impact of membrane composition on Aβ‐membrane interaction becomes essential for the mechanism elucidation of Aβ‐membrane interaction and the early diagnosis of AD. In this work, electrically neutral phosphatidylcholine (PC) as the most major class of membrane phospholipids, including 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphocholine (DPPC), 1,2‐distearoyl‐sn‐glycero‐3‐phosphocholine (DSPC), 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphocholine (POPC), and Aβ(1–40) as the most common amyloid protein were selected as the research subjects, and a developed cantilever‐based biosensor, on which liposomes comprised of PC lipids were immobilized, was applied to characterize in real time the interactions between Aβ(1–40) and membranes comprised of PC lipids with different hydrophobic acyl chains, and to evaluate the effect of cholesterol incorporated in membrane on Aβ‐membrane interaction during the whole process of Aβ(1–40) fibrillization. The results illustrate that the interaction between Aβ(1–40) and PC membrane can be divided into three stages, which are related to the change in molecular states of Aβ. More importantly, it is found that membranes comprised of PC lipids with shorter saturated acyl chains show higher interaction ability with Aβ(1–40), and the incorporation of cholesterol into PC bilayer can remarkably accelerate and strengthen Aβ(1–40)‐membrane interaction. These results confirm that hydrophobicity is the main driving force for the interactions between Aβ(1–40) and PC membranes. In return, the above results enlightened us to apply the current micro‐cantilever immobilized with cholesterol‐containing DPPC liposomes to challenge the detection of low‐concentration Aβ(1–40). This time 50‐nM Aβ(1–40) in aqueous solution has been effectively detected, suggesting that this proposed detection technique would contribute to Aβ detection and early diagnosis of AD in the future.