Taurodeoxycholate Aggregation Explored by Molecular Dynamics: Primary-To-Secondary Micelle Transition and Formation of Mixed Micelles with Fatty Acids

Micelles formed by bile salts in aqueous solution are important for the solubilization of hydrophobic molecules in the gastrointestinal tract. The molecular level information about the mechanism and driving forces for primary-to-secondary micelle transition is still missing. In the current study, the micelle formation of 50 mM solutions of taurodeoxycholate (TDC) is studied by atomistic molecular dynamics simulations. It is shown that primary micelles with an aggregation number of 8-10 emerge and persist within the first 50 ns. Then, they coalesce to form secondary micelles with an aggregation number of 19 molecules. This transition is governed by hydrophobic interactions, which significantly decrease the solvent-accessible surface area per molecule in the secondary micelles. The addition of monomers of the sodium salt of fatty acids (FAs), as agents aiding hydrophobic drug delivery, to secondary TDC micelles results in the co-existence of mixed FA-TDC and pure FA micelles. The studied saturated FAs, with chain lengths of C14:0 and C18:0, are incorporated into the micelle core, whereas TDC molecules position themselves around the FAs, forming a shell on the micelle surface. In contrast, the tails of the C18:1 unsaturated fatty acid mix homogeneously with TDC molecules throughout the entire micelle volume. The latter creates a very suitable medium for hosting hydrophobic molecules in the micelles containing unsaturated fatty acids.