Lipid Membrane Interaction of Peptide/DNA Complexes Designed for Gene Delivery

Among gene delivery systems, peptide-based carriers have received significant attention because of their selectivity, biocompatibility, and biodegradability. Since cellular membranes function as a barrier toward exogenous molecules, cell-penetrating peptides (CPPs), which are usually cationic and/or amphiphilic, can serve efficient to deliver cargo into the cytosol. Here, we examined interactions carrier DNA complexes with lipid using quartz crystal microbalance (QCM) high-speed atomic force microscopy (HS-AFM). The 12-residue partial presequence yeast cytochrome c oxidase subunit IV (Cytcox) BP100, mitochondria-targeting signal peptide CPP, respectively. QCM data showed that BP100 has higher binding affinity than Cytcox both plasma membrane- mitochondrial membrane-mimicking bilayers. either or exhibited same tendency. Furthermore, HS-AFM demonstrated disrupt membranes, forming larger pores in case Cytcox. Our results suggest peptide/DNA complex membrane is more critical its disruption ability enhancing uptake DNA.