Biophysical Society Thematic Meeting

- 21 -

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.