Control of Cell Systems Using Optically-Driven Nanoparticles as Actuators

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DESCRIPTION (provided by applicant): The PI and 3 co-PI's aim to develop new biomedical technology by validating the general principle that externally stimulated nanoparticles can be used as real-time actuators (input transducers) to exert control, perturbation, or regulation of biological systems by external stimuli, e.g. modulated light. Our approach is non-destructive and reversible, intended for information transfer to cells, over long times. Specifically, we aim to provide an experimental demonstration of this general principle, by altering the activity of a well-defined model nervous system using heat produced by light-stimulated gold nanoparticles, thereby causing a spatially localized and fast change in tissue temperature. We will apply gold nanoparticles to electroreceptors of paddlefish, as an experimentally advantageous and well-characterized test system. Our assay for temperature effects will be the frequencies of oscillators contained in each electroreceptor, whose fundamental frequencies (in the range of 20-70 Hz) vary with temperature at 1.8-3.4 Hz/¿C, as we measured previously. Several modes of applying gold nanoparticles will be evaluated to achieve spatially precise heating of different tissue components, including ejection from micropipets, endocytosis, or selective binding to cell surface molecules. Localization will be confirmed by co-delivery of fluorescent labels. We predict, and will evaluate, little toxicity from the gold nanoparticles. We will also test experimentally whether heating from gold nanoparticles can be used to reset the phase synchronization of neural oscillator networks. Quantitative analysis and modeling of heat flows will be used to reconcile our experimental data with the thermal properties of gold nanoparticles and live tissue. RELEVANCE: The proposed research may lead to medical applications, e.g. as a novel means of stimulating or regulating cell systems. This approach may be applicable to a wide range of cell types in the human body, because it is based on purely physical effects.