A drug-lipid interaction model: atropine induces interdigitated bilayer structure

Area of Science:

• Biophysics
• Membrane Biophysics
• Drug Delivery

Background:

• Model membranes, such as dipalmitoylphosphatidylglycerol (DPPG) multilamellar vesicles (MLVs), are crucial for studying drug-lipid interactions.
• Understanding how drugs affect membrane structure is vital for drug development and predicting drug behavior in vivo.

Purpose of the Study:

• To investigate the structural effects of atropine on DPPG MLVs.
• To elucidate the mechanism of atropine-lipid interaction at the molecular level.

Main Methods:

• Small-angle X-ray diffraction was used to analyze structural changes, specifically the lamellar repeating period.
• Fluorescence spectroscopy with probes like 1,6-diphenyl-1,3,5-hexatriene (DPH) assessed membrane fluidity and dynamics.
• Fluorescence polarization using n-(9-anthroyloxyl)-stearic acid (nAS) and 16-(9-anthroyloxyl)-palmitic acid (16AP) provided insights into membrane order and acyl chain packing.

Main Results:

• Atropine incorporation significantly decreased the lamellar repeating period of DPPG MLVs from 5.89 nm to 4.52 nm.
• A notable reduction in DPH fluorescence intensity was observed within a narrow atropine concentration range.
• The typical polarization gradient from nAS and 16AP experiments vanished in the DPPG/atropine system, indicating altered membrane packing.

Conclusions:

• Atropine induces a structural transition from a non-interdigitated to an interdigitated phase in DPPG vesicles within the gel phase.
• These findings establish a robust model for understanding drug-lipid interactions and their impact on membrane structure.