Brownian dynamics simulations of DNA complexation with nano-cationic dendrimers

Abstract

Gene therapy holds a promise in treating genetic diseases by directly delivering therapeutic DNA into living cells. Although viruses have been shown to be efficient delivery vectors, their toxicity has limited their general use. As an alternative, polyamidoamine (PAMAM) dendrimers are considered to be ideal candidates for synthetic vectors due to their unique intrinsic biophysical properties. At neutral pH, a PAMAM dendrimer is cationic and can effectively bind to negatively charged nucleic acid strands to form efficient transfection complexes. In this work, we carried out multiple Brownian dynamics simulations to investigate the physicochemical properties of DNA-PAMAM dendrimers complexes for different lengths of single- and double- stranded DNA complexed with various generations of PAMAM dendrimer. PAMAM dendrimer is represented by a positively charged sphere whereas a bead-spring model is used to model DNA strands. Our results indicate that the formation of DNA-dendrimer complexes is affected by the salt concentration. At low salt concentration (10- 100mM) a DNA chain wraps strongly around the dendrimer, whereas the stronger electrostatics screening effects at high salt concentration limit the wrapping of DNA chain around dendrimers. Furthermore, the morphologies of the aggregates depend on the interaction between DNA and PAMAM dendrimer as well as the PAMAM generation number. For example, G2 with dsDNA seems to have a rodlike structure while ssDNA with G4 trends to give a piece of toroid. Also the flexible dsDNA can form toroidal morphologies with G2 dendrimers while the aggregates of G2 dendrimers and the stiff dsDNA have rod-like structure.