Nanoscale Chemical Imaging of Human Cell Membranes Using Tip-Enhanced Raman Spectroscopy

Lack of appropriate tools for visualizing cell membrane molecules at the nanoscale in a non-invasive and label-free fashion limits our understanding of many vital cellular processes. Here, we use tip-enhanced Raman spectroscopy (TERS) to visualize the molecular distribution in pancreatic cancer cell (BxPC-3) membranes in ambient conditions without labelling, with a spatial resolution down to ca. 2.5 nm. TERS imaging reveals segregation of phenylalanine-, histidine-, phosphatidylcholine-, protein-, and cholesterol-rich BxPC-3 cell membrane domains at the nm length-scale. TERS imaging also showed a cell membrane region where cholesterol is mixed with protein. Interestingly, the higher resolution TERS imaging revealed that the molecular domains observed on the BxPC-3 cell membrane are not chemically "pure" but also contain other biomolecules. These results demonstrate the potential of TERS for non-destructive and label-free imaging of cell membranes with nanoscale resolution.