Control of Cell Systems Using Optically-Driven Nanoparticles as Actuators

描述（由申请人提供）：PI和3个共同PI旨在通过验证外部刺激的纳米颗粒可用作实时致动器（输入换能器）的一般原理来开发新的生物医学技术，以通过外部刺激（例如调制光）对生物系统进行控制、扰动或调节。我们的方法是非破坏性和可逆的，旨在长时间将信息传递到细胞。具体来说，我们的目标是提供一个实验证明这一一般原则，通过改变一个明确的模型神经系统的活动，使用光刺激的金纳米粒子产生的热量，从而导致组织温度的空间定位和快速变化。我们将金纳米粒子应用于白鲟的电感受器，作为一个实验上有利的和良好的测试系统。我们对温度效应的分析将是每个电感受器中包含的振荡器的频率，其基频（在20-70 Hz的范围内）随温度在1.8-3.4 Hz/℃下变化，正如我们之前测量的那样。将评估应用金纳米颗粒的几种模式，以实现不同组织成分的空间精确加热，包括从微量移液管喷射，内吞作用或选择性结合细胞表面分子。将通过荧光标记的共同递送来确认定位。我们预测，并将评估，从金纳米粒子的毒性很小。我们还将通过实验测试金纳米颗粒的加热是否可以用来重置神经振荡器网络的相位同步。热流的定量分析和建模将用于使我们的实验数据与金纳米颗粒和活组织的热特性相一致。相关性：拟议的研究可能会导致医学应用，例如作为刺激或调节细胞系统的新方法。这种方法可能适用于人体中广泛的细胞类型，因为它是基于纯粹的物理效应。

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.