On the formation of dendrimer/nucleolipids surface films for directed self-assembly

We describe the formation and structure of nucleolipid/dendrimer multilayer films controlled by non-covalent interactions to obtain biomaterials that exhibit molecular recognition of nucleic acids. Layers of cationic poly(amidoamine) (PAMAM) dendrimers of generation 4 and the anionic nucleolipids 1,2-dilauroyl-sn-glycero-3-phosphatidylnucleosides (DLPNs) based on uridine (DLPU) and adenosine (DLPA) were first formed at the silica-water interface. The PAMAM/DLPN layers were then exposed to short oligonucleotides, polynucleotides and single stranded DNA (ssDNA). The interfacial properties were characterized using quartz crystal microbalance with dissipation monitoring, attenuated total reflection Fourier transform infrared spectroscopy and neutron reflectometry. Both types of DLPN were found to adsorb as aggregates to preadsorbed PAMAM monolayers with a similar interfacial structure and composition before rinsing with pure aqueous solution. Nucleic acids were found to interact with PAMAM/DLPA layers due to base pairing interactions, while the PAMAM/DLPU layers did not have the same capability. This was attributed to the structure of the DLPA layer, which is formed by aggregates that extend from the interface towards the bulk after rinsing with pure solvent, while the DLPU layer forms compact structures. In complementary experiments using a different protocol, premixed PAMAM/DLPN samples adsorbed to hydrophilic silica only when the mixtures contained positively charged aggregates, which is rationalized in terms of electrostatic forces. The PAMAM/DLPA layers formed from the adsorption of these mixtures also bind ssDNA although in this case the adsorption is mediated by the opposite charges of the film and the nucleic acid rather than specific base pairing. The observed molecular recognition of nucleic acids by dendrimers functionalized via non-covalent interactions with nucleolipids is discussed in terms of biomedical applications such as gene vectors and biosensors.