Wang, Qiuming; Shah, Nilam; Zhao, Jun; Wang, Chengshan; Zhao, Chao; Liu, Lingyun; Li, Lingyan; Zhou, Feimeng; Zheng, Jie
Structural, morphological, and kinetic studies of beta-amyloid peptide aggregation on self-assembled monolayers
PHYSICAL CHEMISTRY CHEMICAL PHYSICS, 13:15200-15210, 2011

The misfolding and aggregation of beta-amyloid peptides (A beta) into amyloid fibrils, a process that has been pathologically linked to the onset of Alzheimer's disease, is dependent on the presence of a heterogeneous surface (e.g., cell membrane). Understanding of the kinetics of amyloid fibril formation and associated structural transition from monomers to intermediates and eventually to fibrils is critical for the development of viable therapeutic agents. In this work, using circular dichroism (CD), atomic force microscopy (AFM), surface plasmon resonance (SPR), and molecular dynamics (MD) simulations, we studied the adsorption, aggregation, and conformational changes of A beta(1-42) from fresh monomers to fully grown fibrils on four model self-assembled monolayers (SAMs): hydrophobic CH3-terminated SAM, hydrophilic OH-terminated SAM, negatively charged COOH-terminated SAMs, and positively charged NH2-terminated SAM. The seeding effect of A beta(1-42) on the kinetics of A beta aggregation on different SAMs is also examined. The CD, AFM, and SPR data show that all of these SAMs greatly accelerate the formation of beta-sheets and amyloid fibrils through surface-enhanced interactions, but A beta(1-42) peptides preferentially adsorb on a hydrophobic CH3-SAM and a positively charged NH2-SAM with much stronger interactions than on a hydrophilic OH-SAM and a negatively charged COOH-SAM. MD simulations further reveal that hydrophobic interactions present a general driving force for Ab adsorption on all SAMs. As A beta aggregates grow into larger species by packing hydrophobic C-terminals to form a hydrophobic core while exposing hydrophilic and negatively charged N-terminals to solution, electrostatic interactions become more strengthened when they interact with the SAMs especially for the COOH-SAM and the NH2-SAM. Thus, both hydrophobic and electrostatic interactions contribute differently to different A beta-SAM systems and to different aggregation stages. A postulated mechanism is proposed to describe the structure and kinetics of A beta aggregation from aqueous solution to the SAMs, providing valuable insights into A beta aggregation on biological cell membranes.

DOI:10.1039/c1cp21156k

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