Modeling Lipid Vesicles’ Dynamic Response to Osmotic Pressure to Quantify Small-Molecule Transport

Proper analysis of the results allows the determination of permeant species’ permeability coefficients. A numerical algorithm was developed to simulate label-free liposome swelling/shrinking assays by explicitly considering the permeant’s water/membrane partition equilibrium and diffusion through the lipid membrane, besides the elastic properties of the latter. Optical density kinetics were collected for gradients of potassium chloride and a series of molecules with different permeability coefficients.

The simulation code (adaptable also to fluorescence data) was iteratively coupled to a least-squares curve-fitting script to retrieve the permeability coefficient. The algorithm proved reliable, yielding results consistent with the literature. It represents both an analysis method and a useful screening tool, as shown by a series of numerical experiments.

The study demonstrated a remarkable difference in sensitivity between swelling and shrinking directions. Although foreseen by theory, this system response asymmetry is not always included in other models, whereas it can make a great difference and must be considered when setting up experiments.