Structural and Mechanical Properties of Amyloid Beta Fibrils: A Combined Experimental and Theoretical Approach

被引：26

作者：

Paul, Thomas J. ^{[1
]}

Hoffmann, Zachary ^{[1
]}

Wang, Congzhou ^{[2
]}

Shanmugasundaram, Maruda ^{[3
]}

DeJoannis, Jason ^{[4
]}

Shekhtman, Alexander ^{[3
]}

Lednev, Igor K. ^{[3
]}

Yadavalli, Vamsi K. ^{[2
]}

Prabhakar, Rajeev ^{[1
]}

机构：

[1] Univ Miami, Dept Chem, Coral Gables, FL 33146 USA

[2] Virginia Commonwealth Univ, Dept Chem & Life Sci Engn, Richmond, VA 23284 USA

[3] SUNY Albany, Dept Chem, Albany, NY 12222 USA

[4] Dassault Syst BIOVIA, San Deigo, CA 92121 USA

来源：

JOURNAL OF PHYSICAL CHEMISTRY LETTERS | 2016年 / 7卷 / 14期

基金：

美国国家科学基金会;

关键词：

EXPERIMENTAL CONSTRAINTS; FORCE MICROSCOPY; ALZHEIMERS; PROTEIN; PEPTIDE; BIOMATERIALS; AGGREGATION; SCAFFOLDS; NANOWIRES; MODEL;

D O I：

10.1021/acs.jpclett.6b01066

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

In this combined experimental (deep ultraviolet resonance Raman (DUVRR) spectroscopy and atomic force microscopy (AFM)) and theoretical (molecular dynamics (MD) simulations and stress-strain (SS)) study, the structural and mechanical properties of amyloid beta (A beta 40) fibrils have been investigated. The DUVRR spectroscopy and AFM experiments confirmed the formation of linear, unbranched and beta-sheet rich fibrils. The fibrils (A beta 40)(n), formed using n monomers, were equilibrated using all-atom MD simulations. The structural properties such as beta-sheet character, twist, interstrand distance, and periodicity of these fibrils were found to be in agreement with experimental measurements. Furthermore, Young's modulus (Y) = 4.2 GPa computed using SS calculations was supported by measured values of 1.79 +/- 0.41 and 3.2 +/- 0.8 GPa provided by two separate AFM experiments. These results revealed size dependence of structural and material properties of amyloid fibrils and show the utility of such combined experimental and theoretical studies in the design of precisely engineered biomaterials.

引用

页码：2758 / 2764

页数：7

共 76 条

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