PAMAM6 dendrimers and DNA: pH dependent "beads-on-a-string" behavior revealed by small angle X-ray scattering

TL;DR

This study investigates how PAMAM6 dendrimers induce DNA self-assembly and wrapping, revealing pH-dependent structural phases and providing insights into DNA-polycation interactions relevant for chromatin modeling.

Contribution

It presents the first detailed SAXS analysis of DNA-PAMAM6 assemblies, demonstrating pH-dependent phase transitions and a DNA wrapping scenario at different pH levels.

Findings

Dense phases form with 2D and 3D hexagonal lattices at different dendrimer concentrations.

DNA wraps around PAMAM6 at pH 5.5, indicating a pH-dependent wrapping behavior.

Structural phases depend on pH and dendrimer charge ratio.

Abstract

DNA interactions with polycations are not only important for our understanding of chromatin compaction but also for characterizing DNA-binding proteins involved in transcription, replication and repair. DNA is known to form several types of liquid-crystalline phases depending, among other factors, on polycation structure and charge density. Theoretical studies and simulations have predicted the wrapping of DNA around spherical positively charged polycations. As a potential mimic of the histone octamer or other DNA wrapping proteins, poly(amido amine) generation 6 (PAMAM6) dendrimers have been chosen for our study. The self-assembly of DNA induced by PAMAM6 has been investigated using small angle X-ray scattering (SAXS) in order to reveal the assemblies' structure dependence on the pH of the environment and on dendrimers concentration. We demonstrate that at pH 8.5 dense phases are formed and characterized by a 2D-columnar hexagonal lattice which is transformed into a 3D hexagonal lattice with increasing dendrimer concentration (charge ratio N/P). Moreover, a systematic analysis of the scattering data collected from diluted samples at pH 8.5 and 5.5 have led us to propose a wrapping scenario of DNA around PAMAM6 at pH 5.5.