De novo amyloid peptides with subtle sequence variations differ in their self-assembly and nanomechanical properties

Proteinaceous amyloids are well known for their widespread pathological roles but lately have emerged also as key components in several biological functions. The remarkable ability of amyloid fibers to form tightly packed conformations in a cross & beta;-sheet arrangement manifests in their robust enzymatic and structural stabilities. These characteristics of amyloids make them attractive for designing proteinaceous biomaterials for various biomedical and pharmaceutical applications. In order to design customizable and tunable amyloid nanomaterials, it is imperative to understand the sensitivity of the peptide sequence for subtle changes based on amino acid position and chemistry. Here we report our results from four rationally-designed amyloidogenic decapeptides that subtly differ in hydrophobicity and polarity at positions 5 and 6. We show that making the two positions hydrophobic renders the peptide with enhanced aggregation and material properties while introducing polar residues in position 5 dramatically changes the structure and nanomechanical properties of the fibrils formed. A charged residue at position 6, however, abrogates amyloid formation. In sum, we show that subtle changes in the sequence do not make the peptide innocuous but rather sensitive to aggregation, reflected in the biophysical and nanomechanical properties of the fibrils. We conclude that tolerance of peptide amyloid for changes in the sequence, however small they may be, should not be neglected for the effective design of customizable amyloid nanomaterials.

Automated summary

Proteinaceous amyloids have important roles in pathology and are also key components in biological functions. Amyloid fibers have robust enzymatic and structural stabilities due to their ability to form tightly packed conformations. Understanding the sensitivity of peptide sequence to subtle changes is crucial for designing customizable amyloid nanomaterials. Small changes in the sequence can affect the aggregation and nanomechanical properties of the fibrils formed by the amyloid peptides. Therefore, considering the tolerance of amyloid peptides to sequence changes is essential for effective design of customizable amyloid nanomaterials.