Tunable Design for Co-Assembly of Coiled-Coil Fibers Using Oppositely Charged Peptides

Self-assembling peptide fibers have many applications, including tissue engineering, drug delivery, and environmentally friendly textile materials. However, previous studies used peptides that self-assemble, limiting their potential for large-scale synthesis. In the current study, three peptides were designed: a negatively charged 21-residue peptide (21n), a negatively charged 28-residue peptide (28n), and a positively charged 35-residue peptide (35p). Peptides of opposite charges that were exposed to each other co-assembled into α-helical coiled-coils. Peptides of different lengths allow for the formation of sticky ends, encouraging linear growth. The peptides include cysteine residues to stabilize fiber growth. Circular dichroism confirmed stable alpha-helical secondary structure, and aggregation assays were conducted to track the assembly of higher-order structures. Transmission electron microscopy was used to visually examine the aggregates that formed. When mixed, the designed peptides co-assembled into large, fibrous aggregates. These fibers were resistant to heat and salt, but they disassembled when exposed to a reducing agent such as dithiothreitol (DTT). Fibers made by pairing 21n or 28n to 35p resulted in different morphologies upon co-assembly under oxidizing conditions. Peptides that are soluble independently but co-assemble into large, disulfide-reinforced fibers present a new platform for tunable, biologically inspired fibers.