Mammalian Cell Surface Imaging with Nitrile-Functionalized Nanoprobes:  Biophysical Characterization of Aggregation and Polarization Anisotropy in SERS Imaging

Abstract

Functionalized silver nanoparticles (NPs) were synthesized with a cyano probe and utilized to label the surface of HeLa cells expressing a recombinant transmembrane domain of the platelet-derived growth factor receptor. Optical imaging, high-resolution Raman imaging, and scanning electron microscopy (SEM) were used to characterize the surface enhanced Raman scattering (SERS) effect at the cell membrane. Different assemblies of NPs resulted in markedly different enhancement. We validated the necessity of NP aggregates and polarization dependency for optimal contrast enhancement in SERS cellular imaging. We demonstrated the ability to image membrane proteins on cells using a cyano-labeled SERS probe. Observed SERS hot-sites correlate well with small aggregated NPs. Furthermore, the strongest SERS signals result from aggregates oriented in the appropriate direction with respect to the incident laser polarization. These observations are critical for designing future molecular imaging agents for SERS imaging of cells and tissues.