Quantum Dot-Functionalized Extracellular Matrices for In Situ Monitoring of Cardiomyocyte Activity

Quantum dots (QDs) have been hypothesized as potential probes for the optical monitoring of electrogenic cell activity given their high optical absorption cross sections compared to organic fluorophores, high brightness, and low photobleaching. Despite the theoretical predictions, less than a handful of papers reported QD-based imaging of cell activity responses because of the critical membrane localization requirements for membrane voltage sensing. Moreover, to the best of our knowledge, two-photon imaging of cellular activity-dependent QD photoluminescence was never demonstrated. The high spatial and temporal resolutions and higher penetration depths, inherent to nonlinear light–tissue interactions, are particularly interesting for biological imaging. In this work, we functionalized fibrous collagen matrices with semiconductor QDs and thereby created artificial extracellular matrices that can optically report cardiomyocyte contractile activity based on QD two-photon fluorescence. We have applied these optically addressable nanofiber matrices to monitor the contractile activity of primary cardiomyocytes, and, for validation, we compared the optical responses with the simultaneously recorded patch-clamp data. Given the long-term stability of QD fluorescence, near-infrared excitation, and high spatiotemporal resolution achievable through multiphoton imaging, this approach can be used for continuous monitoring of cellular functions in cardiac tissue constructs.