Engineering nanoscale optical transducers of mechanical signals in the nervous system

Communication between cells in the nervous system regulates the senses, memory, and information processing. Using electrical and biochemical sensors, such as patch clamps, voltage-sensitive dyes, and calcium-sensitive dyes, scientists have mapped with extraordinary detail the interactions of the nervous system. While the electrical and biochemical signals of neurons are incredibly important for the function of the nervous system there is another signal which is critical and much less explored: mechanical signals. For example, to form connections dendrites, push into the surroundings with picoNetwons of force (a picoNetwon is about one-trillionth of the force needed to stand), healthy neurons also maintain a steady tension, and during development picoNewton forces define the folds formed in the brain. Abnormalities of mechanical forces are a signature of disease and malfunction.

While mechanical forces play a critical role in a healthy nervous system, it is currently challenging to detect them with current state-of-the-art sensors. The goal of this project is to engineer a new type of mechanical force sensor, based on upconverting nanoparticles (UCNPs) to probe sub-nanoNewton forces created and felt by neurons. UCNPs consist of ceramic particles doped with lanthanides (in this proposal’s case Yb3+ and Er3+). They operate by absorbing multiple low energy infrared photons and emitting higher energy visible photons. Applying a mechanical force to the UCNPs causes them to emit more red photons than green photons. Using this ratio-color metric, we can map 10s of nanoNewton forces. During the course of this post-doc, I will characterize the mechanical response of single particles, engineer them to be sensitive to sub-nanoNewton forces, and test their bio-sensing capabilities by incorporating them with C. elegans, a model system. These particles will be non-invasive mechanical force sensors for scientists to map the mechanical signaling of the nervous system.