Self-assembly and structure transformations in living polymers forming fibrils

A generic statistical mechanical model is presented for the selfassembly of chiral rod-like units, such as ␤-sheet-forming peptides, into helical tapes, which with increasing concentration associate into twisted ribbons (double tapes), fibrils (twisted stacks of ribbons), and fibers (entwined fibrils). The finite fibril width and helicity is shown to stem from a competition 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. The behavior of two rationally designed 11-aa residue peptides, P 11-I and P11-II, is illustrative of the proposed scheme. P11-I and P11-II are designed to adopt the ␤-strand conformation and to selfassemble in one dimension to form antiparallel ␤-sheet tapes, ribbons, fibrils, and fibers in well-defined solution conditions. The energetic parameters governing self-assembly have been estimated from the experimental data using the model. The 8-nm-wide fibrils consist of eight tapes, are extremely robust (scission energy Ϸ200 kBT), and sufficiently rigid (persistence length lfibril Ϸ 20 -70 m) to form nematic solutions at peptide concentration c Ϸ 0.9 mM (volume fraction Ϸ0.0009 vol͞vol), which convert to self-supporting nematic gels at c > 4 mM. More generally, these observations provide a new insight into the generic self-assembling properties of ␤-sheet-forming peptides and shed new light on the factors governing the structures and stability of pathological amyloid fibrils in vivo. The model also provides a prescription of routes to novel macromolecules based on a variety of self-assembling chiral units, and protocols for extraction of the associated energy changes.P rospects for the large-scale production of low-cost peptides by genetic engineering (1) open up new opportunities for exploiting protein-like self-assembly as a route to novel biomolecular materials (2-5). In this context, the small-oligopeptide route has distinct processing advantages over the use of longer polypeptides. Previously, we have demonstrated that oligopeptides can be designed to self-assemble into micrometer-long ␤-sheet tapes (6). We now wish to show that, as a consequence of the amino acid chirality, an entire hierarchy of twisted self-assembling macromolecular structures is accessible, with tapes as the most primitive form: ribbons, fibrils, and fibers. These polymers are shown to give rise to nematic fluids and gels at concentrations determined by the characteristic flexibility and length of each type of polymer.The type of molecular assembly we discuss and exemplify here arises not only in the context of desirable engineered biomaterials, but also in pathological self-assembly of mis-folded proteins, when the aggregated assemblies are referred-to as ''amyloids.'' A very wide class of proteins may be induced into producing the tapefibril-fiber sequence of structures (7) We present a theoretical model that enables the morphology and properties of thes...

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“…5, 6, 8, 9, and 10) are asymptotic. The detailed theory generalizing the classic isodesmic model (12) has been published separately (13).…”

Section: Methodsmentioning

confidence: 99%

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

Aggeli

Nyrkova²,

Bell³

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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1,051

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“…Theoretical models of self-assembled peptide fibers have been divided into three categories, depending on the level of scalings involved: first, a molecular model [32 •• ]; second, a semi-continuum model, where the self-assembled structure is treated as an elastic tape composed of brick-like building blocks [4 •• ,6 • , 33,34]; and third, a fully continuum, field-theoretic model [35]. Each contributes to part of the overall understanding.…”

Section: Nm Current Opinion In Chemical Biologymentioning

confidence: 99%

Design of nanostructured biological materials through self-assembly of peptides and proteins

Zhang

Marini

Hwang

et al. 2002

Current Opinion in Chemical Biology

552

361

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“…Under specific conditions, these peptides undergo one-dimensional self-assembly, forming micrometer-long, l3-sheet "nanotapes". Further assembly can then be induced, such that the nanotapes stack in pairs to form ribbons (Nyrkova et al, 2000b;Aggeli et al, 2001b), which in tum can further assemble to form fibrils ( Fig. 1), and pairs of fibrils entwine edge-to-edge to form fibers.…”

Section: Introductionmentioning

confidence: 99%

Self-assembling Peptide Scaffolds Promote Enamel Remineralization

Kirkham

Firth²,

Vernals³

et al. 2007

J Dent Res

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310

314

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Rationally designed l3-sheet-forming peptides that spontaneously form three-dimensional fibrillar scaffolds in response to specific environmental triggers may potentially be used in skeletal tissue engineering, including the treatment/prevention of dental caries, via bioactive surface groups. We hypothesized that infiltration of caries lesions with monomeric low-viscosity peptide solutions would be followed by in situ polymerization triggered by conditions of pH and ionic strength, providing a biomimetic scaffold capable of hydroxyapatite nucleation, promoting repair. Our aim was to determine the effect of an anionic peptide applied to caries-like lesions in human dental enamel under simulated intra-oral conditions of pH cycling. Peptide treatment significantly increased net mineral gain by the lesions, due to both increased remineralization and inhibition of demineralization over a five-day period. The assembled peptide was also capable of inducing hydroxyapatite nucleation de novo. The results suggest that self-assembling peptides may be useful in the modulation of mineral behavior during in situ dental tissue engineering.

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Self-assembly and structure transformations in living polymers forming fibrils

Cited by 92 publications

References 2 publications

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

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

Design of nanostructured biological materials through self-assembly of peptides and proteins

Self-assembling Peptide Scaffolds Promote Enamel Remineralization

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