Fermi Resonant Interaction of the Tailed Methyl Groups of Langmuir Monolayer at the Air/Water Interface during Phase Transition

Molecular insight into the interactions of two-dimensional (2D) materials at the interface is essential to understand the functionality of interfacial molecular devices. Yet it still remains elusive so far. Fermi resonant interaction is highly sensitive to the total molecular interactions. In this study, we used lipid 1,2-dimyristoyl-<i>sn</i>-glycero-3 -phospho-(1′-rac-glycerol) (sodium salt) (DMPG) monolayer as a model, and performed a systematic study to investigate the Fermi resonant interactions of 2D materials at the interface during liquid-expanded (LE) to liquid-condensed (LC) phase transition using multiplexed-polarization sum frequency generation vibrational spectroscopy (SFG-VS). It is found that the ratio (<i>R</i>₁) between Fermi resonance and symmetric stretching mode of the tailed methyl groups sharply decreases during the phase transition. The sharp drop of <i>R</i>₁ originates from the nonsynchronous change of the tail and head groups of the lipid. The tailed CH₃ groups of DMPG locally accumulate at the air/water interface during LE–LC phase transition while the head glycerol groups do not. The local aggregation of the methyl groups strengthens the van der Waals (vdW) interaction, leading to the decrease of the total intermolecular interactions and the drop of the ratio of <i>R</i>₁. However, such phenomena are not observed at the air/KCl solution (0.3M) interface

Interfacial Structure and Transformation of Guanine-Rich Oligonucleotides on Solid Supported Lipid Bilayer Investigated by Sum Frequency Generation Vibrational Spectroscopy

Lipid membrane-anchored guanine-rich oligonucleotides with non-Watson–Crick structures can perform structure transformation in a controllable and reversible manner upon the external stimuli. Elucidating the mechanisms of their interaction and transformation is the key to understand medical applicability and functioning feasibility of these oligonucleotides. In this study, the molecular structure and interfacial transformation kinetics of guanine-rich oligonucleotides at model cell membrane were investigated by sum frequency generation vibrational spectroscopy (SFG-VS) in real time and <i>in situ</i>. The conformations of oligonucleotides are obtained by analyzing the SFG spectra in the “fingerprint” region. The results indicate that the electrostatic interaction and hydrophobic interaction are both important to the interfacial adsorption and transformation of oligonucleotides. The tilt angles of oligonucleotides with different conformations were also calculated. Molecular insights into interfacial oligonucleotides will help researchers to control the oligonucleotide–lipid membrane interactions in a desired manner and improve the reproductivity, stability, and reversibility of oligonucleotide-based applications

Intermolecular Interactions at the Interface Quantified by Surface-Sensitive Second-Order Fermi Resonant Signals

Accurate determination of intermolecular interaction forces at the surface and the interface is essential to identify the nature of interfacial phenomena such as absorption, interfacial assembly, and specific ion effect, but it still represents a major technical challenge. In this study, we proposed a novel method to deduce the interfacial interaction forces by using surface-sensitive second-order Fermi resonant signals, generated in sum frequency generation vibrational spectroscopy (SFG-VS). By investigating the influence of lipid chain length and intermolecular distance on the Fermi resonant signals of phospholipid monolayer at the air/CaF₂ surface and the air/water interface, a linear correlation between the Fermi resonant intensity ratio and the dominated interactions in the lipid monolayer has been observed. It implies that the amplitude of the intensity ratio can be used as an effective <i>in situ</i> vibrational optical ruler to characterize the total intermolecular interaction forces at the surface and the interface. Such a relationship further enables us to elucidate the specific ion effects on the interfacial interactions, allowing us to identify different contributions from van der Waals, electrostatic, and hydration interactions. This study clearly demonstrates the power of the second-order Fermi resonant signals for evaluating the interfacial interaction forces <i>in</i> <i>situ</i> and in real time

Amide III SFG Signals as a Sensitive Probe of Protein Folding at Cell Membrane Surface

A good understanding of membrane protein folding at the molecular level requires an effective means to determine the dynamical structural changes on coil-to-helix transition within the cell membrane and as yet remains challenging. Herein, we demonstrate that the amide III spectral signals of the protein backbone, generated in the sum frequency generation vibrational spectroscopy, are a powerful tool to probe the protein folding processes within the membrane in situ, in real time, and without exogenous labels. The amide III signals are capable of separating the spectral profiles of the random-coil and α-helical structures at the interface. The intensity ratio of coil and helix peaks becomes a prime indicator that allows one to directly capture the dynamical change of the coil–helix transition. With this approach, using pardaxin as a model, the influence of lipid charge on the peptide folding degree at the cell membrane surface has been nicely elucidated. It is evident that the negative charge of the lipid increases the folding degree of pardaxin upon interfacial adsorption and promotes the formation of α-helical structure during the insertion of peptides into the lipid bilayer. This robust spectral approach can thus greatly enhance our ability to monitor the dynamics of membrane proteins in a real cell environment in situ

In Situ and Real-Time SFG Measurements Revealing Organization and Transport of Cholesterol Analogue 6‑Ketocholestanol in a Cell Membrane

Cholesterol organization and transport within a cell membrane are essential for human health and many cellular functions yet remain elusive so far. Using cholesterol analogue 6-ketocholestanol (6-KC) as a model, we have successfully exploited sum frequency generation vibrational spectroscopy (SFG-VS) to track the organization and transport of cholesterol in a membrane by combining achiral-sensitive ssp (ppp) and chiral-sensitive psp polarization measurements. It is found that 6-KC molecules are aligned at the outer leaflet of the DMPC lipid bilayer with a tilt angle of about 10°. 6-KC organizes itself by forming an α–β structure at low 6-KC concentration and most likely a β–β structure at high 6-KC concentration. Among all proposed models, our results favor the so-called umbrella model with formation of a 6-KC cluster. Moreover, we have found that the long anticipated flip-flop motion of 6-KC in the membrane takes time to occur, at least much longer than previously thought. All of these interesting findings indicate that it is critical to explore in situ, real-time, and label-free methodologies to obtain a precise molecular description of cholesterol’s behavior in membranes. This study represents the first application of SFG to reveal the cholesterol–lipid interaction mechanism at the molecular level