Oligonucleotide-Based Amphiphilic Block Copolymers Interacting with Cell Membrane Models at the Air-Water Interface

Abstract

Oligonucleotides have exceptional molecular recognition properties, which are involved in biological mechanisms such as gene silencing or cell-surface receptor recognition. In many cases, the cell membrane structure is barrier to investigate their use in human therapy for drug or gene delivery. However, this can be obviated by grafting a hydrophobic tail to the oligonucleotide. In this present work, we demonstrate that two oligonucleotides, one consisting of 12 guanosine units (G12), and the other one consisting of five adenosine and seven guanosine (A5G7) units, when functionalized with poly(butadiene), namely PB-G12 and PB-A5G7, can be incorporated into Langmuir monolayers of dipalmitoyl phosphatidyl choline (DPPC), which served as a cell membrane model. With surface pressure and surface potential-area isotherm, we observed that PB-G12 and PB-A5G7 affect the DPPC monolayer, even at high values of surface pressure. The effects from PB-G12 were consistently stronger, particularly in reducing the surface compressibility of the DPPC monolayers, which may have important biological implications. Multilayers of DPPC and nucleotide-based copolymers could be transferred onto solid supports, in the form of Y-type Langmuir-Blodgett films, in which the molecular-level interactions led to lower energies in the vibrational spectra of the nucleotide-based copolymers. The successful deposition of solid films opens the way for devices to be produced which exploit the molecular recognition properties of the nucleotides.