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

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• 作者：Thomas J. Paul ; Zachary Hoffmann ; Congzhou Wang ; Maruda Shanmugasundaram ; Jason DeJoannis ; Alexander Shekhtman ; Igor K. Lednev ; Vamsi K. Yadavalli ; Rajeev Prabhakar
• 刊名：The Journal of Physical Chemistry Letters
• 出版年：2016
• 出版时间：July 21, 2016
• 年：2016
• 卷：7
• 期：14
• 页码：2758-2764
• 全文大小：466K
• 年卷期：0
• ISSN：1948-7185

文摘

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 (Aβ40) fibrils have been investigated. The DUVRR spectroscopy and AFM experiments confirmed the formation of linear, unbranched and β-sheet rich fibrils. The fibrils (Aβ40)_n, formed using n monomers, were equilibrated using all-atom MD simulations. The structural properties such as β-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.