Peptide self-assembly has been used to design an array of nanostructures with functional applications in biomedicine, such as drug delivery. Experimental studies have reported the self-assembly of peptide-based drug amphiphiles (DAs) into stable nanotube structures. Here, each DA is composed of four anticancer drugs, camptothecin (CPT), conjugated to a short peptide via a biodegradable disulphide linker. The DA-nanotube possesses hydrophilic and charged peptides on the surface of the tube, protecting the hydrophobic CPT that lines the inner surface of the tube, with an inner channel of water. However, it is difficult to experimentally characterize the interaction of these nanotubes with the cell membrane at the molecular level. Herein, we characterize the interaction of the DA-nanotube with a model cell membrane with advanced sampling methods using all-atomistic molecular dynamics. We calculate the potential of mean force using umbrella sampling as a function of the distance between the center of mass of the nanotube and the center of mass of the membrane. Preliminary results suggest that the DA-nanotube has a very strong repulsive interaction that can induce a huge bending fluctuation in the membrane. We next characterize the change of the properties of the membrane with respect to its interaction with the nanotube. These results provide important insight into the rational design of bio-functional supramolecular nanostructures.

Interaction of supramolecular anticancer nanotubes with model cell membranes

2019 Spring National Meeting

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