Fatty Acid Deaggregation and Extraction from Vesicles by Serum Albumin Proceeds Via a Dock-and-Load Mechanism.

It is unknown whether the transport protein serum albumin extracts fatty acid (FA) monomers from aggregates and causes deaggregation. We studied the effect of human and bovine serum albumin on spin-labeled FAs 5/16-DOXYL stearic acid in phospholipid vesicles, in mixtures with decanoic acid (DA), and as pure aggregates. With continuous-wave electron paramagnetic resonance (CW EPR) spectroscopy, we distinguished and quantified free, aggregated, and albumin-bound FAs by their rotational dynamics, local concentrations, and polarities under different conditions. Our study unveils complex triangular equilibria between albumin and monomeric and aggregated FAs. The EPR spectra and altered aggregate sizes observed via dynamic light scattering confirm albumin-aggregate interactions. These argue for a dock-and-load FA transfer mechanism of albumin, while the binding of free FAs induces deaggregation. Similar effects on protein- or polymer-based aggregates could affect their use as drug carriers and guide future strategies in drug delivery or in the treatment of aggregation-related diseases.