Biophysical Society Thematic Meeting - October 25-30, 2015

Polymers and Self Assembly: From Biology to Nanomaterials

Tuesday Speaker Abstracts

Nanomechanics of Amyloid-Like Polymers Made of Self-Assembled Mouse Prion Proteins Guillaume Lamour , Calvin Yip, Hongbin Li, Joerg Gsponer. University of British Columbia, Vancouver, BC, Canada. Amyloids are made of several polypeptides of the same protein that self-assemble into highly- ordered fibrillar nanostructures characterized by a cross-beta sheet conformation. Their outstanding mechanical properties combined with great thermodynamic stability make them excellent candidates for the development of future biomaterials with nanotechnological applications. Amyloids were first discovered in the context of brain pathologies. They are involved in infectious prion diseases (e.g., mad cow disease, Creutzfeldt-Jakob), but they also play a role in noninfectious nonprion diseases (e.g. Parkinson's, Alzheimer's). What distinguishes amyloid fibrils formed by prions from those formed by other proteins is not clear. On the basis of previous studies on yeast prions that correlated high intrinsic fragmentation rates of fibrils with prion propagation efficiency, it has been hypothesized that the nanomechanical properties of prion amyloid such as elastic modulus and strength may be the distinguishing feature. Here, we demonstrate that fibrils formed by mammalian prions are relatively soft (0.1-1GPa) and clearly in a different class of rigidities when compared to nanofibrils formed by nonprions (over 2GPa). Using a new bimodal nanoindenting technique of atomic force microscopy called AM-FM mode, we estimated the radial modulus of PrP fibrils at lower than 0.6GPa, consistent with the axial moduli derived by using an ensemble method (built upon polymer physics equations that calculate the persistence length by measuring fibril shape fluctuations). We also show, by using sonication-induced fibril scission, that the mechanical strength of prions fibrils (10-150MPa) is significantly lower than that of nonprions (250-800MPa). Our results have far-reaching implications for the understanding of protein-based infectivity and the design of future amyloid biomaterials. Reference: Lamour et al. ACS Nano. 2014. pubs.acs.org/doi/abs/10.1021/nn5007013

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