REDUCING THE INTERACTION BETWEEN AMYLOID β AND MEMBRANE BY CHANGING LIPID PACKING DENSITY

• Main Authors: Pin-Chiuan Chiou, 邱品銓
• Other Authors: Yi-Fan Chen
• Format: Others
• Language: en_US
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/59vm3u

碩士 === 國立中央大學 === 化學工程與材料工程學系 === 105 === Amyloid β (Aβ) peptides are the major component of the proteinaceous plaques prevalent in the brains afflicted with Alzheimer's disease (AD), and therefore have long drawn researchers’ close attention in their efforts to develop effective diagnostics and therapeutics for AD. While past researches had focused on the aggregation behavior of Aβ and its suppression, some very recent studies have pointed to the pathogenic relevance of the interactions between Aβ and neuronal membranes, thus paving a new way for the related researches. Here, to help address many unresolved questions regarding the Aβ-membrane interactions, we adopt the binary liposomes composed of phosphatidylcholine and phosphatidylglycerol as model systems and modulate their molecular packing densities by changing the types (i.e., lengths and saturation) of the hydrocarbon chains of the lipids to investigate how changes in the physical property of a membrane affect the interactions between the membranes and Aβ in different aggregation states. Remarkably, while the membranes with less tight and ordered packing are susceptible to the structural disturbances induced by oligomeric Aβ (>30 kDa), through the formation of pore-like structures, as imaged with the atomic force microscopy (AFM), the membranes cannot be disintegrated by the Aβ-membrane interactions with ease. In contrast, the membranes with the lipids packed more tightly and orderly are thickened and readily disintegrated by Aβ, as revealed by the X-ray scattering and fluorescent leakage assays combined with AFM, respectively. These findings demonstrate that the packing density of a membrane is a key determinant of the Aβ-membrane interactions. Since the lipid compositions of human neuronal membranes change with age, which raises the packing density of the membranes, our findings may underlie the clinical observation that the incidence of AD increases sharply with age. Increasing the amount of unsaturated phospholipid or even reversing the trend of tight packing of the membrane might constitute a way of fighting AD.