Engineering β-Sheet Peptide Coassemblies for Biomaterial Applications

Abstract

Peptide coassembly, wherein at least two different peptides interact to form multicomponent nanostructures, is an attractive approach for generating functional biomaterials. Current efforts seek to design pairs of peptides, A and B, that form nanostructures (e.g., β-sheets with ABABA-type β-strand patterning) while resisting self-assembly (e.g., AAAAA-type or BBBBB-type β-sheets). To confer coassembly behavior, most existing designs have been based on highly charged variants of known self-assembling peptides; like-charge repulsion limits self-assembly while opposite-charge attraction promotes coassembly. Recent analyses using solid-state NMR and coarse-grained simulations reveal that preconceived notions of structure and molecular organization are not always correct. This perspective highlights recent advances and key challenges to understanding and controlling peptide coassembly.

Distinct neurotoxic TDP-43 fibril polymorphs can be generated by heterotypic interactions with α-synuclein

“…Hybrid heterotypic aggregates thus far have not been observed among amyloid proteins except for a select few atypical amyloid systems (77)(78)(79)(80). PrLD-αS hybrid fibrils shown here and in our previous study (52) form the first among the class of hybrid heterotypic amyloid fibrils.…”

“…On the other hand, co-aggregation is a process of synergistic aggregation of two different amyloid protein monomers towards heterotypic hybrid fibrils containing both proteins. Hybrid heterotypic aggregates thus far have not been observed among amyloid proteins except for a select few atypical amyloid systems (77–80). PrLD–αS hybrid fibrils shown here and in our previous study (52) form the first among the class of hybrid heterotypic amyloid fibrils.…”

The rippled β-sheet layer configuration—a novel supramolecular architecture based on predictions by Pauling and Corey

“…Our findings inspired us to explore the possibility of making a quasi-racemic rippled β-sheet fibril as proof of concept for an [A:B] n array, a potentially useful design principle for peptidic materials. 6 An equimolar mixture of the FWF l -tripeptide and the fyf d -tripeptide was crystallized, and yielded needles containing periodic [FWF:fyf] n rippled antiparallel β-sheet layers, in which the l - and the d -tripeptides were found to strictly alternate ( Fig. 4 and S4 † ).…”

“…The rippled b-sheet layer configuration-a novel supramolecular architecture based on predictions by Pauling and Corey † Introduction Tailored proteins and peptides hold immense potential for materials development and biomedical application. Chiral (i.e., D-amino acid) substitutions may be employed to generate selfassembling peptide architectures with unique properties, [1][2][3][4][5][6] bioactive compounds with distinct activities, [7][8][9][10][11][12][13] as well as systems with enhanced crystallization behavior. [14][15][16][17][18] There is great interest in developing new peptidic systems that contain Damino acid substitutions, as this would allow systematic access to a vast structural space with unique molecular properties.…”

Distinct neurotoxic TDP-43 fibril polymorphs are generated by heterotypic interactions with α-Synuclein

“…On the other hand, coaggregation is a process of synergistic aggregation of two different amyloid protein monomers toward heterotypic hybrid fibrils containing both proteins. Hybrid heterotypic aggregates thus far have not been observed among amyloid proteins except for a select few atypical amyloid systems ( 79 , 80 , 81 , 82 ). PrLD–αS hybrid fibrils shown here and in our previous study ( 52 ) form the first among the class of hybrid heterotypic amyloid fibrils.…”