Monte-Carlo simulations of PAMAM dendrimer–DNA interactions

Abstract

We use Monte Carlo simulations to determine the influence of poly(amido amine) (PAMAM) dendrimer size and charge on its interactions with double-stranded DNA conformation and interaction strength. To achieve a compromise between simulation speed and molecular detail, we combine the coarse-grained DNA model of de Pablo et al. which resolves each DNA base using three beads - and thereby retains the double-helix structure - with a dendrimer model with resolution similar to that of the DNA. The resulting predictions of the effects of dendrimer generation, dendrimer surface charge density, and salt concentration on dendrimer-DNA complexes are in agreement with both experiments and all-atom MD simulations. The model predicts that DNA wraps a fully charged G5 or G6 dendrimer at low salt concentration (10 mM) similarly to a histone octamer, and for the G5 dendrimer, DNA super helices with both handednesses occur. At salt concentrations above 50 mM, or when a high fraction of dendrimer surface charges are neutralized by acetylation, DNA adheres but does not compactly wrap the dendrimer, in agreement with experimental findings. We are also able to simulate pairs of dendrimers binding to the same DNA strand. Thus, our mesoscale simulation not only elucidates dendrimer-DNA interactions, but also provides a methodology for efficiently simulating chromatin formation and other cationic macroion-DNA complexes.

Computer Simulation of DNA Condensation by PAMAM Dendrimer

“…However, the R g of the ssDNA molecule and the ssDNA-G4 PAMAM complex both increase monotonically when solution salt concentration is increased, because of the reduced binding affinity between the ssDNA and dendrimer at the higher salt concentration. Our R g values for the complexes as well as of the ssDNA molecules and dendrimers in those complexes are similar to the Monte Carlo (MC) result, [52] but it is worth noting that a dsDNA of 38 base pairs length is used to bind dendrimer of different generations in the MC simulation.…”

Ultrasound-enhanced gene delivery to alfalfa cells by hPAMAM dendrimer nanoparticles

“…However, there are few reports on the utilization of dendrimers as gene delivery carriers for plant cells (Pasupathy et al, 2008). The interaction of DNA with dendrimers (dendriplex formation) and its condensation by the dendrimers depends on several factors, such as the N/P (charge) ratio and the dendrimers' generation (Lee and Larson, 2006;Yu and Larson, 2014). It has been reported that the smaller G2 PAMAMs, due to their more fluid structure, could bind to DNA better than the larger G6 PAMAMs (Kabanov et al, 2000).…”

Biophysical Correlates on the Composition, Functionality, and Structure of Dendrimer–Liposome Aggregates

“…20,21 Charge and size mainly govern the strength of dendrimer function. 22 Positively charged dendrimers interact more effectively with cell membranes or other model bilayer carrying net negative charge because of obvious reasons. Since the first successful production of poly(amidoamine) (PAMAM) dendrimer in the mid-1980s, 23,24 dendrimers have received significant attention.…”