Impact of DNA Sequence and Structure on Polyelectrolyte Complex Micelle Morphology

Polyelectrolyte complex micelles (PCMs) are promising nucleic acid nanocarriers; however, nucleic acids are usually treated as generic polyanions, leaving the impact of nucleotide sequence and partially hybridized structures unclear. Here, we systematically tune DNA stiffness in PCMs using (i) single-stranded sequences with varied purine contents and (ii) hybridization structures in the form of hairpins, single-tailed duplexes, and double-tailed duplexes. Small-angle X-ray scattering, electron microscopy, and dynamic light scattering reveal a strong bending penalty imposed by increasing DNA stiffness that drives a transition from spherical to less-curved cylindrical or worm-like PCMs with ordered cores. Increasing the purine content produces gradual morphological changes, whereas hybridized constructs show sharper transitions. We further link the availability of base-stacking sites to the cylindrical PCM length and see that longer rigid DNA results in higher stiffness of cylindrical PCMs. The results establish relationships connecting the DNA sequence, structure, and polymer length to PCM morphology.