(391b) Growth Behavior of Amyloid Fibrils on Membrane Interfaces of Lipid Membranes

Amyloid β protein (Aβ) that is a small peptide (4.5 kDa) forms amyloid fibrils and is a possible causative factor for Alzheimerâ??s disease. Morphology of fibrils is one of key factors in determining its cytotoxicity¹⁾. Liposome is a closed lipid bilayer membrane composed of phospholipids and provides the variety of morphologies of Aβ fibrils²⁾. The fibril growth behavior was likely to depend on the interfacial properties of liposome such as the charge, hydrophobicity, or membrane fluidity. The initial step where Aβ binds to and accmulates on liposome membranes has been clarified, to some extent ^3,4). Meanwhile, the relationship between the initial step for the growth of amyloid fibrils and their morphologies has been still unclear. In this study, we investigated the relationship between the accumulation step of Aβ on lipid membranes and the growth process, in the molecular aspects.<span">In the observation with a time-of-flight secondary imaging mass spectroscopy (ToF-SIMS), an invasion of Aβ into 1,2-oleoyl-sn-glycero-3-pospocholine (DOPC) membrane with high fluidity and a deposit of Aβ on 1,2-palmitoyl-sn-glycero-3-pospocholine (DPPC) membrane with low fluidity were confirmed. The accumulation pattern of Aβ obtained by ToF-SIMS were consistent with the result obtained from other spectroscopic methods. Morphology of fibrils on lipid membranes was also characteristic: fibrils formed on DPPC membranes were short, straight and rigid whereas fibrils on DOPC membrane were branched. This growth behavior indicated the environment of lipid membranes being obstacle for elongation of fibrils. Therefore, the position of Aβ accumulation in/on lipid membranes appeared to determine the extent that the environment of lipid membranes such as headgroup mobility or laerall difusion of lipid molecules influeced the elongation process of fibrils.

1) R. Roychaudhuri et al., J. Biol Chem, 284, 4749-4753 (2009)

2) T. Shimanouchi et al., AIChE J., 58, 3625-3632 (2012)

3) K. Matsuzaki et al., Biochim. Biophys. Acta 1768, 1935-1942(2007)

4) M. Terakawa-Suzuki et al., J. Biol. Chem., 290, 815-826 (2015)