Supramolecular Peptide Nanofibrils with Optimized Sequences and Molecular Structures for Efficient Retroviral Transduction

Amyloid-like peptide nanofibrils (PNFs) are abundant in nature providing rich bioactivities and playing both functional pathological roles. The structural features responsible for their unique are, however, still elusive. Supramolecular nanostructures notoriously challenging to optimize, as sequence changes affect self-assembly, fibril morphologies, biorecognition. Herein, the first optimization of PNFs, derived from enhancing factor-C (EF-C, QCKIKQIINMWQ), enhanced retroviral gene transduction via a multiparameter multiscale approach is reported. Retroviral transfer method choice stable delivery genetic information into cells offering great perspectives treatment disorders. Single imaging, zeta potential, vibrational spectroscopy, quantitative assays provide structure parameters PNF assembly, fibrils morphology, secondary quaternary structure, PNF-virus-cell interactions. Optimized sequences such 7-mer, CKFKFQF, have been obtained quantitatively forming supramolecular with high intermolecular β-sheet content that efficiently bind virions attach cellular membranes revealing efficient transfer.