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Biological and Environmental Phenomena at the Interface
Gel Phase Membrane Retards Amyloid #-peptide (1-42) Fibrillation by Restricting Slaved Diffusion of Peptides on Lipid Bilayers Mengting Yang, Kang Wang, Jiake Lin, Liqun Wang, Feng Wei, Jin-Tao Zhu, Wanquan Zheng, and Lei Shen Langmuir, Just Accepted Manuscript • DOI: 10.1021/acs.langmuir.8b01315 • Publication Date (Web): 20 Jun 2018 Downloaded from http://pubs.acs.org on June 21, 2018
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Langmuir
Gel Phase Membrane Retards Amyloid β-peptide (1-42) Fibrillation by Restricting Slaved Diffusion of Peptides on Lipid Bilayers Mengting Yang,†∆ Kang Wang,‡∆ Jiake Lin,‡ Liqun Wang,§ Feng Wei,*§ Jintao Zhu,† Wanquan Zheng,§,# Lei Shen*‡ † School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan 430070, China ‡ School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan 430074, China § Institute for Interdisciplinary Research & Key Laboratory of Optoelectronic Chemical Materials and Devices of Education, Jianghan University, Wuhan 430056, China # Institute des Sciences Moléculaires d’Orsay, Université Paris-Sud, 91405Orsay Cedex, France
ABSTRACT: Plasma membranes in the human brain can interact with amyloid β-peptide (1-42) (Aβ42) and induce Aβ42 fibrillation, which is considered to be a crucial process underlying the neurotoxicity of Aβ42 and the pathogenesis of Alzheimer’s disease (AD). However, the mechanism of membrane-mediated Aβ42 fibrillation at the molecular level remains elusive. Here we study the role of adsorbed Aβ42 peptides on membrane-mediated fibrillation using supported lipid bilayers of varying phase structures (gel and fluid). Using total internal reflection fluorescence microscopy and interfacial specific second-order nonlinear optical spectroscopy, we show that the dynamics of 2D-mobile Aβ42 molecules, facilitated by the highly mobile lipids underneath the peptides, are critical to Aβ42 fibrillation on liquid phase membranes. This growth mechanism is retarded on gel phase membranes where the dynamics of 2D-mobile peptides are restricted by the “frozen” lipids with less mobility.
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These authors contribute equally to this work.
Introduction
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The fibrillation of amyloid β-peptides (Aβ) as senile plaques around neuronal cells is considered to be implicated in the pathogenesis of Alzheimer’s disease (AD). As a cleavage product of β- and γ-secretase upon the transmembrane amyloid precursor protein (APP), Aβ molecules, with a length range of 38–42 amphiphilic residues, can misfold from their native conformations, assemble into oligomerized nucleus and, eventually, elongate into β-sheet filamentous aggregates. In a cellular environment, Aβ fibrillation can be initiated by cell membranes through their nonspecific interactions with Aβ molecules. 1 - 3 In addition, Aβ aggregates can exert cytotoxicity through associations with neuronal cells, leading to membrane thinning, pore formation and fragmentation. 4 , 5 Therefore, it is significant to investigate Aβ interaction with membranes that is a fundamental phenomenon with potential implications for AD pathogenesis. One of the main characterizations in AD pathogenesis is the abnormal decrease of membrane fluidity, a parameter that reflects the membrane phase structure (gel or fluid), in the brain cortex and hippocampal neurons of AD patients.6-10 Although the changes of membrane fluidity have been demonstrated to significantly affect cellular functioning and downstream signal transductions,11 it is difficult to prove the early stage of membrane fluidity change and its role in AD pathogenesis. Recent studies have indicated the special importance of membrane fluidity when considering membrane interactions with Aβ molecules once extracellularly cleaved from APP in the membrane. For example, both experimental studies 12-16 and molecular dynamics simulations17 show that Aβ molecules and their aggregates can significantly change membrane fluidity even at small amount of peptide (
