Nanoscale Chemical Imaging of Supported Lipid Monolayers using Tip‐Enhanced Raman Spectroscopy

Abstract

Visualizing the molecular organization of lipid membranes is essential to comprehend their biological functions. However, current analytical techniques fail to provide a non-destructive and label-free characterization of lipid films under ambient conditions at nanometer length scales. In this work, we demonstrate the capability of tip-enhanced Raman spectroscopy (TERS) to probe the molecular organization of supported DPPC monolayers on Au (111), prepared using the Langmuir–Blodgett (LB) technique. High-quality TERS spectra were obtained, that permitted a direct correlation of the topography of the lipid monolayer with its TERS image for the first time. Furthermore, hyperspectral TERS imaging revealed the presence of nanometer-sized holes within a continuous DPPC monolayer structure. This shows that a homogeneously transferred LB monolayer is heterogeneous at the nanoscale. Finally, the high sensitivity and spatial resolution down to 20 nm of TERS imaging enabled reproducible, hyperspectral visualization of molecular disorder in the DPPC monolayers, demonstrating that TERS is a promising nanoanalytical tool to investigate the molecular organization of lipid membranes.