Feb 14, 2014
Unlocking the strength of amyloid fibrils
Amyloid fibrils are a broad class of misfolded self-assembling protein structures with impressive mechanical properties. Despite being known for their role in diseases such as Alzheimer’s disease, Parkinson’s disease and type II diabetes, they are increasingly showing potential for use in functional roles. Here, researchers at MIT have used molecular dynamics simulations to understand the origins of these properties and guide the development of amyloid-based functional biomaterials.
Amyloid fibrils are among the strongest and stiffest protein structures known. These useful mechanical properties are known to originate in the secondary structures of these fibrils. However there are many different specific amyloid proteins that exhibit a variety of structural motifs, or secondary structures, at the molecular scale. This causes the complex problem of choosing an optimal amyloid protein for an application out of hundreds or thousands of potential proteins. As shown in the image, all share a characteristic beta-sheet motif, but the precise molecular arrangement varies between different types: from simple stacked arrangements to more complex helical configurations. The relationship between the specific geometry and the mechanical properties of these protein fibrils, including tensile strength and deformation and failure mechanisms, was not well understood until this report in Nanotechnology.
Deformation is geometrically independent
The researchers at MIT found that in general, the deformation and failure mechanisms of amyloid fibrils are independent of the specific geometry of the fibril. For small deformations, the hydrogen bonds in the fibrils work cooperatively to provide the characteristic high strength; as the deformation is further increased, multiple hydrogen bonds rupture in rapid succession and the stress in the fiber drops off significantly. The deformation process then shifts to one in which the remaining hydrogen bonds break one-by-one and provide almost zero additional tensile strength, much like a crack propagating through a brittle material.
Strength is geometrically dependent
In contrast, the specific strength of the amyloid fibrils is found to be quite dependent on the specific structure of the fibrils. Geometries that can accommodate a higher density of hydrogen bonds into the fibril cross-section achieve a much higher strength since they allow more hydrogen bonds to work together to enhance the mechanical response.
This report provides several simple yet important insights into structure-property relationships in amyloid protein materials. Most notably, all of the structures tested feature very similar deformation and failure mechanisms. The molecular geometries which maximize the areal hydrogen bond density result in the strongest amyloid fibrils, therefore the problem of choosing an amyloid protein is reduced to finding those with structures that do this. This work also lays the groundwork for a consistent framework for choosing amyloid proteins for use in novel functional materials including composites, biofilms and adhesives.
Additional details can be found in the Journal Nanotechnology 25 105703
About the author
Max Solar is a Ph.D. candidate at the Massachusetts Institute of Technology (MIT) in the Department of Materials Science and Engineering, and a member of the Laboratory for Atomistic and Molecular Mechanics . Professor Markus Buehler leads the Laboratory for Atomistic and Molecular Mechanics at MIT and is the Head of the Department of Civil and Environmental Engineering. His research focuses on multiscale modeling of biological and bio-inspired materials, including amyloids and other proteins.