A coupled proton-transfer and twisting-motion fluorescence probe for lipid bilayers

Area of Science:

• Biophysics
• Materials Science
• Chemical Biology

Background:

• Lipid bilayers are crucial biological structures whose physical properties influence cellular functions.
• Monitoring structural changes in lipid bilayers is essential for understanding membrane dynamics and drug delivery.
• Existing probes may have limitations in sensitivity or specificity for bilayer analysis.

Purpose of the Study:

• To introduce a new molecular probe, 2-(2 e-hydroxyphenyl)imidazo[1, 2-a]pyridine (HPIP), for sensitive detection of lipid bilayer structural alterations.
• To characterize the photophysical behavior of HPIP within various lipid vesicle compositions.
• To establish HPIP as a reliable tool for quantifying the physical properties of lipid bilayers.

Main Methods:

• Synthesis and characterization of the HPIP molecular probe.
• Spectroscopic analysis (fluorescence spectroscopy) of HPIP in model lipid vesicles (DMPC, DPPC) with and without cholesterol.
• Investigation of HPIP's photoinduced intramolecular proton-transfer and twisting motion upon electronic excitation.
• Correlation of fluorescence parameters with lipid bilayer structural and dynamic changes.

Main Results:

• HPIP exhibits a large Stokes-shifted fluorescence band dependent on its twisting motion within lipid bilayers.
• The probe's fluorescence is sensitive to changes in lipid composition, temperature, and cholesterol content.
• HPIP's fluorescence in vesicles is distinct from its aqueous fluorescence, enabling selective monitoring.
• Static and dynamic fluorescence parameters of HPIP effectively report on bilayer physical properties.

Conclusions:

• HPIP is a sensitive and photostable molecular probe for monitoring structural and dynamic changes in lipid bilayers.
• The probe's mechanism, involving proton transfer and twisting motion, is well-suited for probing bilayer environments.
• HPIP offers a promising tool for investigating membrane biophysics and the physical properties of lipid-based systems.