TY - JOUR
T1 - Structural and Mechanical Properties of Amyloid Beta Fibrils
T2 - A Combined Experimental and Theoretical Approach
AU - Paul, Thomas J.
AU - Hoffmann, Zachary
AU - Wang, Congzhou
AU - Shanmugasundaram, Maruda
AU - Dejoannis, Jason
AU - Shekhtman, Alexander
AU - Lednev, Igor K.
AU - Yadavalli, Vamsi K.
AU - Prabhakar, Rajeev
N1 - Funding Information:
This work was supported by the National Science Foundation under Grant No. CHE-1152752 (I.K.L.). Financial support from the James and Esther King Biomedical Research Program of the Florida State Health Department (DOH grant number 08KN-11) to R.P. is gratefully acknowledged. Computational resources from the Center for Computational Science at the University of Miami are greatly appreciated.
Publisher Copyright:
© 2016 American Chemical Society.
PY - 2016/7/21
Y1 - 2016/7/21
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.jpclett.6b01066
DO - 10.1021/acs.jpclett.6b01066
M3 - Article
AN - SCOPUS:84979642904
VL - 7
SP - 2758
EP - 2764
JO - Journal of Physical Chemistry Letters
JF - Journal of Physical Chemistry Letters
SN - 1948-7185
IS - 14
ER -