Interactions of Novel Phosphonium Dye with Lipid Bilayers: A Fluorescence Study

Abstract

The phosphonium-based optical probes attract ever growing interest due to their excellent chemical and photophysical stability, high aqueous solubility, long wavelength absorption and emission, large extinction coefficient, high fluorescence quantum yield, low cytotoxicity, etc. The present study was focused on assessing the ability of the novel phosphonium dye TDV to monitor the changes in physicochemical properties of the model lipid membranes. To this end, the fluorescence spectral properties of TDV have been explored in lipid bilayers composed of zwitterionic lipid phosphatidylcholine (PC) and its mixtures with cholesterol (Chol) or/and anionic phospholipid cardiolipin (CL). It was observed that in the buffer solution TDV possesses one well-defined fluorescence peak with the emission maximum at 533 nm. The dye transfer from the aqueous to lipid phase was followed by the enhancement of the fluorescence intensity coupled with a red shift of the emission maximum up to 67 nm, depending on the liposome composition. The quantitative information about the dye partitioning into lipid phase of the model membranes was obtained through approximating the experimental dependencies of the fluorescence intensity increase vs lipid concentration by the partition model. Analysis of the partition coefficients showed that TDV has a rather high lipid-associating ability and displays sensitivity to the changes in physicochemical properties of the model lipid membranes. The addition of CL, Chol or both lipids to the PC bilayer gives rise to the increase of the TDV partition coefficients compared to the neat PC membranes. The enhancement of the phosphonium dye partitioning in the CL and Chol-containing lipid bilayers has been attributed to the cardiolopin- and cholesterol-induced changes in the structure and physicochemical characteristics of the polar membrane region.

Interactions of Novel Phosphonium Dye with Lipid Bilayers: A Molecular Dynamics Study

“…Specifically, it was demonstrated that TDV can be effectively used for optical detection of disease-related protein aggregates [54,55] and for elucidating the mechanisms of DNA interactions with amyloid fibrils [56]. Moreover, it was shown previously that TDV is highly suitable for membrane studies since it possesses a pronounced lipid-associating ability and high sensitivity to physicochemical properties of the model lipid bilayers [57].…”

“…In the present study the molecular dynamics simulation was used to explore the interaction between TDV and the model lipid membranes with the main emphasis on determining the depth of the probe location in a lipid bilayer. Besides, it was assumed previously that membrane electrostatics plays an important role in the membrane association of TDV [57]. Therefore, it was also interesting to assess the role of TDV charge in the dye membrane partitioning.…”