Molecular Structure and Interactions of Lipids in the Outer Membrane of Living Cells Based on Surface-Enhanced Raman Scattering and Liposome Models

The distribution and interaction of lipids determine the structure and function of the cellular membrane. Surface-enhanced Raman scattering (SERS) is used for selective molecular probing of the cell membrane of living fibroblast cells grown adherently on gold nanoisland substrates across their whole contact areas with the substrate, enabling mapping of the membrane’s composition and interaction. From the SERS data, the localization and distribution of different lipids and their interactions, together with proteins in the outer cell membrane, are inferred. Interpretation of the spectra is mainly supported by comparison with the spectra of model liposomes composed of phosphatidylcholine, sphingomyelin, and cholesterol obtained on the same gold substrate. The interaction of the liposomes with the substrate differs from that with gold nanoparticles. The SERS maps indicate colocalization of ordered lipid domains with cholesterol in the living cells. They support the observation of ordered membrane regions of micrometer dimensions in the outer leaflet of the cell membrane that are rich in sphingomyelin. Moreover, the spectra of the living cells contain bands from the groups of the lipid heads, phosphate, choline, and ethanolamine, combined with those from membrane proteins, as indicated by signals assigned to prenyl attachment. Elucidating the composition and structure of lipid membranes in living cells can find application in many fields of research.