We explored how sequence and structure of DNA controls the shape of polyelectrolyte complex micelles. By tuning DNA stiffness through purine content and partial hybridization, we found that more rigid nucleic acids favor elongated cylindrical and worm-like nanostructures instead of spherical particles. Using SAXS, TEM, DLS, and DENSS reconstructions, we developed structure-property relationships providing new design rules for nucleic acid polymer self-assembly. Our work was published in ACS Biomacromolecules!

We investigated why double-stranded RNA is unusually resistant to polyelectrolyte complexation and how its ionic environment can be used to overcome that barrier. Unlike ssRNA, ssDNA, and dsDNA, dsRNA failed to consistently assembly with poly(L-lysine) under standard low-salt conditions, which we attribute to its rigid A-form helix, high local charge density, and deep major groove. By introducing divalent salts including Mg2+ and Ca2+, we see complexation occur between dsRNA + Lysine, supported by SAXS, TEM, microscopy, and all-atom molecular dynamic simulations. 

We showed how chemical modifications to the nucleic acid backbone alters polyelectrolyte complex formation, structure, and stability. By comparing DNA, RNA, and 2'-O'methyl RNA with and without phosphorothiote substitution, we found that seemingly small chemical changes can dramatically reshape assembly behavior. For example, phosphorothioate modifications increased complex stability by up to ~5-fold and promoted dsRNA complexation. 

We explored how polycation chemistry controls the formation and salt stability of dsRNA and polyelectrolyte compelxes. By systematically varying stereochemistry, charged-group chemistry, side-chain structure, hydrophobicity, and polymer block length, we found that relatively small changes in polymer molecular structure produces dramitically different dsRNA assembly behavior. In particular, D-lysine stereochemistry and guanidinium-containing polyarginine overcome the low-salt assembly barrier observed with poly(L-lysine), while synthetic polycations exhibit distinct formation and dissolution. These resultts show that complex formation and complex stability are separate design problems and establishes polymer chemistry as a powerful handle for engineering dsRNA materials.

We investigated how mixing kinetics and flow conditions control the self-assembly of polyelectrolyte complex micelles. Using Y-shaped, herringbone, tesla, and ring micromixers, we systemtatically varied flow rate and channel geometry to tune the competition between mixing, electrostatic competition, and polymer rearrangement. Faster flow produced smaller, more uniform, spherical micelles, while slower conditions promoted polydisperse, anisotropic, and kinetically trapped structures. These results establish assembly pathway as a key structure-property variable and demonstrate microfludic mixing as a scalable strategy for controlling PCM size, morphology, and reproducibility.