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The Structures of Fibril Aggregates of Beta-amyloid Peptide 1-40 upon Addition of diC6PC

Tsang-Lang Lin, C.-L. Huang, C.-M. Lin, Heh-Nan Lin
National Tsing-Hua University, TW

Keywords: fibril, beta-amyloid, structure

The amyloid peptides were found to form fibril aggregates in aqueous solutions and the formation of fibril aggregates is thought to be the cause of the Alzheimer's disease [1-2]. It was found that the beta-amyloid 1-42 would form fibril aggregates much faster than the shorter beta-amyloid 1-40 [1]. The diameter and length of the fibril aggregates was found to vary during the growing process. The rate of the fibril growth depends on the concentration, temperature and time of aggregation. Typical diameter of the fibril is in the range of 3 to 8 nm, and the length could reach several microns [2]. The aggregation can be slowed down by adding amphiphilic molecules such as C12E6 at a few mM concentrations [3]. Besides its significance on causing the Alzheimer's disease, the highly stable fibril aggregates of amyloid peptides is an ideal template for growing nanowires. In order to have a better control of the length of the aggregated fibrils, dihexanoylphosphatidylcholine (diC6PC) at 1, 2 and 3 mM were added to 0.1 M HCl solutions containing 0.125 mM beta-amyloid 1-40. As investigated by AFM, Fig. 1 shows the aggregated fibrils without adding the diC6PC at 21 days after preparing the sample. The fibrils grew to several microns in length. The height (diameter) is about 3 to 8 nm. As a comparison, Fig. 2 shows the sample added with 1 mM diC6PC at 21 days. Most of the fibrils have length about 1 micron or shorter. The height (diameter) of the fibrils is about 4 nm. Increasing the concentration of diC6PC to 2 and 3 mM will further reduce the average length of the aggregated fibrils. More accurate monitoring the growth of the fibril was carried out by using the dynamic light scattering. The results were shown in Fig. 3. The pure amyloid peptide solution has the highest rate of growth and grows to 1.4 microns in 28 hours. The addition of 1, 2, and 3 mM diC6PC can reduce the length to about 1.2, 1.0 and 0.9 microns, respectively, at 28 hours after preparation. This shows that the average length can be controlled by adding different amounts of amphiphilic molecules and at the same time the diameter of the fibrils were not significantly changed. [1] J. D. Harper, C. M. Lieber, P. T. Lansbury, Jr., Chemistry & Biology, 4, 951, 1997. [2] J. D. Harper, S. S. Wong, C. M. Lieber, P. T. Lansbury, Jr., Chemistry & Biology, 4, 119, 1997. [3] A. Lomakin, D. S. Chung, G. B. Benedek, D. A. Kirshiner, D. B. Teplow, Proc. Natl. Acad, Sci, 93, 1125, 1996.

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