Imaging Extracellular Protein Concentration with Nanoplasmonic Sensors

Extracellular protein concentrations and gradients queue a wide range of cellular responses, such as cell motility and division. Spatio-temporal quantification of these concentrations as produced by cells has proven challenging. As a result, artificial gradients must be introduced to the cell culture to correlate signal and response. Here we demonstrate a label-free nanoplasmonic imaging technique that can directly map protein concentrations as secreted by single cells in real time and which integrates with standard live-cell microscopes. When used to measure the secretion of antibodies from hybridoma cells, a broad range of time-dependent concentrations was observed: from steady-state secretions of 230 pM near the cell surface to large transients which reached as high as 56 nM over several minutes and then dissipated. The label-free nature of the technique is minimally invasive and we anticipate will enable the quantification of deterministic relationships between secreted protein concentrations and their induced cellular responses.