Qualitative and Quantitative Analyses of the Molecular-Level Interaction between Memantine and Model Cell Membranes

Abstract

Sum frequency generation (SFG) vibrational spectroscopy was employed to study the interaction between memantine (a water-soluble drug for treating Alzheimer's disease) and lipid bilayers (including zwitterionic PC and negatively charged PG lipid bilayers) at the molecular level in real time and in situ. SFG results revealed how the memantine affected these lipid bilayers in terms of the lipid dynamics, average tilt angle (θ), as well as angle distribution width (σ). It was found that memantine could adsorb onto the zwitterionic PC surface but did not affect the flip-flop rate of the PC bilayer even in the presence of 5.0 mM memantine, indicating the negligible interaction between memantine and the PC bilayer. However, for the negatively charged PG bilayer, it was found that the outer PG leaflet could be significantly destroyed by memantine at a relatively low memantine concentration (1.0 mM), while the inner PG leaflet remained intact. Besides, the θ and σ of CD 3 groups in the outer PG lipid leaflet were calculated to be ∼82.0°a nd ∼19.5°after adding 5 mM memantine, respectively, indicating that these CD 3 groups were prone to lie down at the membrane surface (versus the surface normal) with the addition of 5 mM memantine while nearly standing up without the addition of drug molecules. These monolayer-and molecular-level results could hardly be obtained by other techniques. To the best of our knowledge, this is the first experimental attempt to quantify the drug-induced orientational changes of lipid molecules within a lipid bilayer. The present work provided an in-depth understanding on the interaction between memantine and model cell membranes, which will potentially benefit the development of new drugs for neurodegenerative diseases involving drug− membrane interaction.

Observing a Chemical Reaction at a Buried Solid/Solid Interface in Situ

“…However, a weak SFG ppp signal at 1640 cm −1 was observed, indicating that the amide groups were not totally consumed by MAH at the interface. The amine N−H stretching signals completely disappeared after the reaction at the nylon/MAHgEO interface (Figures 1B and 2), which suggests that the remaining amide N−H groups (if any) probably lie in the plane of the buried interface or are randomly oriented, based on the SFG theory, 28,69,70 leading to no detectable signal. Spectra collected from the nylon/EO interface are quite different in the carbonyl CO stretching region than those from the buried nylon/MAHgEO interface (Figure 3B,C).…”

Sum Frequency Generation Vibrational Spectroscopy Using Evanescent Waves—Toward Probing Irregular and Complex Surfaces of Mesoscopic-Scale Materials

“…Sum frequency generation (SFG) vibrational spectroscopy, as a second order nonlinear optical technique developed for more than 30 years since the first series of papers were published in 1987 by Shen et al., − has shown significant advantages over the traditional ones due to its intrinsic surface selectivity and molecular orientation sensitivity. Surface and interfacial molecular-level structures for a wide range of materials have successfully been studied, − providing new knowledges and promoting our understanding on the materials’ surfaces and interfaces. It should be noted, as a coherent process, interaction of the two incident beams with molecules at a flat surface or interface leads to a third sum frequency beam with the defined output direction.…”

Unique Vibrational Features as a Direct Probe of Specific Antigen–Antibody Recognition at the Surface of a Solid‐Supported Hybrid Lipid Bilayer

“…More specifically, second‐order NLO techniques have set one′s heart on biological interfaces for multiple reasons, first of all the possibility to univocally probe those nano‐bio‐interfaces while surrounded by a macroscopic liquid environment, with the unique advantage that the latter does not contribute to the signal . For example, lipid mono‐ or bilayers mimicking cell membranes are still extensively investigated in interaction with peptides or membrane proteins . In addition to fundamental research purposes, second‐order NLO spectroscopies have provided successful proofs in detecting biological recognition in nanoscale devices.…”

“…[9,10,11] For example, lipid mono-or bilayers mimicking cell membranes are still extensively investigated in interaction with peptides or membrane proteins. [12][13][14][15][16][17][18][19][20][21][22][23][24][25] In addition to fundamental research purposes, second-order NLO spectroscopies have provided successful proofs in detecting biological recognition in nanoscale devices. Second harmonic generation (SHG) ands um frequency generation (SFG) probe the electronic and vibrational responses, respectively,o f interfacial systems.…”