Nanomechanical Properties of Human Prion Protein Amyloid as Probed by Force Spectroscopy
Dragomir N. Ganchev 1, Nathan J. Cobb 1, Krystyna Surewicz 1 and Witold K. Surewicz 1*
1 Case Western Reserve University
* To whom correspondence should be addressed. E-mail: witold.surewicz{at}case.edu.
Submitted on March 7, 2008
Revised on April 10, 2008
Accepted on 21 May 2008
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Abstract |
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Amyloids are associated with a number of protein misfolding disorders including prion diseases. Here, we used single molecule force spectroscopy to characterize nanomechanical properties and molecular structure of amyloid fibrils formed by human prion protein PrP90-231. Force-extension curves obtained by specific attachment of a gold-covered atomic force microscope tip to engineered Cys residues could be described by the worm-like chain model for entropic elasticity of a polymer chain, with the size of the N-terminal segment that can be stretched entropically depending on the tip attachment site. The present data provide direct information about forces required to extract an individual monomer from the core of the PrP90-231 amyloid, as well as indicate that the 
-sheet core of this amyloid starts at residue ~164-169. The latter finding has important implications for the ongoing debate regarding the structure of PrP amyloid.
Key Words:
AFM, amyloids, force spectroscopy, prion, single molecule
