(676a) Invited Talk: Towards In Vivo Bioimaging of Electrical Fields and Mechanical Forces with Stimuli-Responsive Upconverting Nanoparticles

Cellular signaling and health are governed in large part by mechanical forces and electromagnetic fields. Mechanical forces play a critical role in cell differentiation, tissue organization, and diseases such as cancer and heart disease, whereas membrane voltage transients (i.e., action potentials) are essential for inter-cellular signaling, muscle contraction, and sensory perception. Accordingly, quantifying a biological system’s forces and fields is crucial for understanding physiology and disease pathology, as well as for developing medical tools for repair and recovery. Here, we introduce a new class of in vivoprobes to monitor biological forces and fields at the organ-to-organism scale with high spatial and temporal resolution. Our design is based on inorganic upconverting nanoparticles that, when excited in the near-infrared, emit light of a different color (wavelength) and intensity in response to sub-100mV electric potentials and nanoNewton-to-microNewton forces. The nanoparticles are sub-20nm in size, do not bleach or photoblink, need not be genetically encoded, and, by virtue of their infrared absorption, can enable deep tissue imaging with minimal tissue autofluorescence and light-induced tissue damage. We present the design, synthesis, and characterization of these nanoparticles both in vitro and in vivo, focusing on the forces generated by the roundworm C. elegansas it feeds and digests its bacterial food. Chronic and acute cytotoxicity assays are also used to confirm biocompatibility. Our force measurements are coupled with electrical measurements of muscle contractions in both wild-type and mutant animals, providing insight into the interplay between mechanical, electrical, and chemical signaling in vivo.