Lipid Landscapes: Vibrational Spectroscopy for Decoding Membrane Complexity

Abstract

Cell membranes are incredibly complex environments containing hundreds of components. Despite substantial advances in the past decade, fundamental questions related to lipid-lipid interactions and heterogeneity persist. This review explores the complexity of lipid membranes, showcasing recent advances in vibrational spectroscopy to characterize the structure, dynamics, and interactions at the membrane interface. We include an overview of modern techniques such as surface-enhanced infrared spectroscopy (SEIRAS) as a steady-state technique with single-bilayer sensitivity, two-dimensional sum-frequency generation (2D SFG) spectroscopy, and two-dimensional infrared (2D IR) spectroscopy to measure time-evolving structures and dynamics with femtosecond time resolution. Furthermore, we discuss the potential of multiscale MD simulations, focusing on recently developed simulation algorithms which have emerged as a powerful approach to interpret complex spectra. We highlight persistent challenges in accurately sampling heterogeneous ensembles in multicomponent membranes. Overall, this review provides an up-to-date comprehensive overview of the powerful combination of vibrational spectroscopy and simulations to illuminate lipid-lipid, lipid-protein, and lipid-water interactions in the intricate conformational landscape of cell membranes.