(794c) Engineering Large Self-Assembled Amyloid Fibers

Amyloid fibers are robust biomaterials capable of self-assembling from a variety of proteins.  It is generally accepted that any protein can assemble into an amyloid structure.  However, few systems have been able to assemble at physiological conditions or to very large length scales.  Here we introduce a system that utilizes peptide mixtures to form large micrometer sized amyloid fibers at near physiological conditions.¹  A short, hydrophobic template peptide interacts with an α-helical adder protein to cooperatively self-assemble into an amyloid fiber.  By altering the in vitro solution conditions and peptides in the mixture it is possible to engineer a fiber with a tailored morphology (rectangular or cylindrical cross-section) and modulus (0.1-2.5 GPa).²  Atomic force microscopy (AFM) shows fiber self-assembly occurs in four stages: 1) peptides self-assemble into elementary protofibrils (width=15-30 nm), 2) protofibrils laterally and vertically stack into fibrils (width=60-120 nm) that 3) aggregate into large fibrils (width=150-480 nm), and upon drying 4) large fibrils assemble into amyloid fibers (width=10-20 μm).³  The type of peptides in the mixture can be varied to initiate morphological and property differentiation after stage 2.  Thus, the hierarchical self-assembly, morphology, and rigidity of the fiber can be designed and predicted based on overall peptide properties in the mixture.  In recent work, we have demonstrated that the fiber morphology and properties can be encoded at the genetic level by re-programming cells to extracellularly express template and adder peptides.    

References

1              Ridgley, D. M., Ebanks, K. C. & Barone, J. R. Peptide Mixtures Can Self-Assemble into Large Amyloid Fibers of Varying Size and Morphology. Biomacromolecules 12, 3770-3779, doi:10.1021/bm201005k (2011).

2              Ridgley, D. M., Claunch, E. C. & Barone, J. R. The effect of processing on large, self-assembled amyloid fibers. Soft Matter 8, 10298-10306, doi:10.1039/c2sm26496j (2012).

3              Ridgley, D. M. & Barone, J. R. Evolution of the Amyloid Fiber over Multiple Length Scales. ACS nano 7, 1006-1015, doi:10.1021/nn303489a (2012).