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The nanomechanical properties of amyloid fibrils using molecular dynamics simulations

University of British Columbia

Amyloid fibril formation, believed to be a generic property of polypeptides, plays major roles in neurodegenerative pathologies such as Alzheimer’s, Parkinson’s and prion diseases, as well as in functional biological processes in many organisms including humans. Revealing specifics of their molecular architecture, conformational stability, mechanisms of formation and physical properties holds clues to devising effective methods to fight their associated pathologies. An increasing requirement has been the development of a detailed understanding of the nanomechanics of amyloid core structures due to their relevance in biomedicine and nanotechnology. Of special significance is the mechanism of fibril fracture and infectivity in disease as well as the mechanical stability for novel biomaterial design. Here, we use a series of steered molecular dynamics simulations on different amyloid fibrils to report a broad spectrum of mechanical properties ranging from a strong and stiff β-helical fibril to weak and soft amyloid such as those formed by the mammalian prion protein. We relate the strength and elastic modulus with hydrogen bond densities and van der Waals energies in the core of the fibrils and show that weakened side-chain interactions lead to fibrils with reduced tensile strengths as a result of modified molecular packing in the fibril core. This modulation might lead to a combination of exceptional mechanical attributes such as those of the human functional amyloids.

Text

2017-04-30

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/57685

Genome Science and Technology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/