Monitoring enzymatic degradation of pericellular matrices through SERS stamping

We introduce a surface enhanced Raman spectroscopy (SERS) stamping approach for acquiring cell-surface specific vibrational spectra of individual living cells under physiological conditions. The SERS stamping approach utilizes a nanostructured metal surface on top of a lithographically defined piston that can be translated in 3-dimensions with nanometer resolution to contact living cells in solution with a pristine metal surface. We applied this approach to characterize the chemical composition of the cellular surface of living MCF7 breast cancer cells and to monitor its change upon addition of the enzyme hyaluronidase, which degrades major constituents of the pericellular matrix. Although the cell surface spectra show significant cell-to-cell fluctuations, a statistical barcode analysis of the spectra ensembles reveals systematic changes in the cell surface SERS spectra upon addition of hyaluronidase, which are consistent with a thinning of the pericellular matrix.