Control of Cell Systems Using Optically-Driven Nanoparticles as Actuators

描述(由申请人提供)：PI和3co-PI的目标是通过验证外部刺激纳米颗粒可用作实时执行器(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(如调制光)对生物系统施加控制、扰动或调节。我们的方法是非破坏性的和可逆的，打算在很长一段时间内将信息传输到细胞。具体地说，我们的目标是提供这一一般原理的实验演示，通过使用光刺激金纳米颗粒产生的热量来改变定义明确的模型神经系统的活动，从而导致组织温度的空间局部化和快速变化。我们将把金纳米颗粒应用于白对虾的电感受器，作为一种具有实验优势和良好特性的测试系统。我们对温度效应的测试将是每个电感受器中包含的振荡器的频率，其基频(在20-70赫兹范围内)在1.8-3.4赫兹/°C的温度下变化，正如我们之前测量的那样。将评估几种应用金纳米颗粒的模式，以实现对不同组织成分的空间精确加热，包括从微管中排出、内吞或选择性结合到细胞表面分子。本地化将通过共同交付荧光标签来确认。我们预测，并将评估，金纳米颗粒的毒性很小。我们还将通过实验测试纳米金加热是否可以用来重置神经振荡器网络的相位同步。我们将使用热流的定量分析和建模来使我们的实验数据与金纳米颗粒和活组织的热性质相一致。相关性：拟议的研究可能导致医学应用，例如作为一种刺激或调节细胞系统的新方法。这种方法可能适用于人体内广泛的细胞类型，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.