Hierarchical self-assembly of chiral rod-like molecules as a model for peptide beta-sheet tapes, ribbons, fibrils, and fibers

A generic statistical mechanical model is presented for the self-assembly o f chiral rod-like units, such as beta -sheet-forming peptides, into helical tapes, which with increasing concentration associate into twisted ribbons (double tapes), fibrils (twisted stacks of ribbons), and fibers (entwined f ibrils). The finite fibril width and helicity is shown to stem from a compe tition between the free energy gain from attraction between ribbons and the penalty because of elastic distortion of the intrinsically twisted ribbons on incorporation into a growing fibril. Fibers are stabilized similarly. T he behavior of two rationally designed 11-aa residue peptides, P-11-I and P -11-II, is illustrative of the proposed scheme. P-11-I and P-11-II are desi gned to adopt the beta -strand conformation and to self-assemble in one dim ension to form antiparallel beta -sheet tapes, ribbons, fibrils, and fibers in well-defined solution conditions. The energetic parameters governing se lf-assembly have been estimated from the experimental data using the model. The 8-nm-wide fibrils consist of eight tapes, are extremely robust (scissi on energy approximate to 200 k(B)T), and sufficiently rigid (persistence le ngth (I) over tilde (fibril) approximate to 20-70 mum) to form nematic solu tions at peptide concentration c approximate to 0.9 mM (volume fraction app roximate to0.0009 vol/vol), which convert to self-supporting nematic gels a t c > 4 mM. More generally, these observations provide a new insight into t he generic self-assembling properties of beta -sheet-forming peptides and s hed new light on the factors governing the structures and stability of path ological amyloid fibrils in vivo. The model also provides a prescription of routes to novel macromolecules based on a variety of self-assembling c ira units, and protocols for extraction of the associated energy changes.