Abstract

Binding between cetyltrimethylammonium bromide, a cationic surfactant, and a variety of lengths of single stranded DNA was measured using fluorescence polarization and a simple cooperative model was used to obtain dissociation constants on the order of 1 × 10−5 for the aggregates that formed. Aggregation depended on strand length where strands much shorter than 40 nucleotides (for example strands of 24-nucleotides) were too short to form the same size aggregates. Other factors such as salt concentration and temperature also affected aggregate formation: increasing either the salt concentration or performing binding at the highest temperature studied (60 °C) made it more difficult for aggregates to form. Both heating and dilution of aggregates caused the anisotropy signal to decrease, which suggested that the complexes fell apart under these conditions. Force spectroscopy of aggregate surfaces showed that both electrostatic and hydrophobic adhesive forces were present between aggregates and derivatized AFM tips. These findings can be used to better understand the stability of cationic surfactant-DNA aggregates and may provide guidance for lipid nanoparticle design used in vaccine development and therapeutics.

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