EAGER Collaborative Research: Towards Wireless Nano-Electrostimulation of Ion Channels in Mammalian Cells.

这项探索性研究的目标是开发一种利用纳米级电场远程刺激哺乳动物细胞的技术。这个新概念利用了多铁纳米粒子的磁电特性，当受到外部磁场脉冲时，它可以在细胞膜附近产生局部电场。这些电场有望控制电压门控离子通道的功能，电压门控离子通道是电压敏感的大分子，负责Na+， K+离子在细胞膜上的运输。为了阐明这种新方法的可行性，PI将利用新奥尔良大学先进材料研究所的计算机模拟和薄膜技术来设计和制造纳米电极和多铁粒子的图案阵列，以产生纳米级电场。离子通道对纳米电刺激的反应将由Co-PI在新奥尔良洛约拉大学的生物物理实验室使用改进的膜片钳技术进行测量。由于新方法的未来体内应用将涉及使用磁性和铁电纳米粒子的多铁纳米复合材料，Co-PI还将设计铁电纳米粒子的递送方法，并将确定其毒性和与哺乳动物细胞的结合。这项合作研究将有效地利用新奥尔良大学和洛约拉大学在物理学、材料科学和生物物理学方面的资源和专业知识。智力优势：这项提议的研究是利用多铁纳米粒子的磁电特性作为无线探针来电刺激哺乳动物细胞的尝试。外界纳米级电场对哺乳动物细胞中离子传输的影响尚未被研究过，本研究将有助于更好地了解细胞的基本功能。尽管对磁性纳米颗粒在生物系统中的应用进行了广泛的研究，但对铁电纳米颗粒与哺乳动物细胞的相互作用知之甚少，拟议的研究将阐明铁电材料及其复合材料在生物医学应用的可行性。研究人员将开发细胞内和细胞外递送纳米粒子的新方法，并改进膜片钳技术，以测试活细胞中离子通道对频率高达5 kHz的外加磁场的响应。脉冲的序列以及纳米粒子的特性将被调整，以确定对离子电流的控制。更广泛的影响：本研究的结果预计将对生物学、医学、生物技术和仿生学等多个学科产生深远影响。利用磁场脉冲成功控制离子输运，为治疗离子通道相关疾病（如囊性纤维化、糖尿病、心律失常、神经和精神疾病、胃肠道疾病、心血管疾病和高血压）提供了另一种非侵入性方法。由于电压门控离子通道负责神经元动作电位的触发和传播，刺激离子通道的新机制可用于治疗疼痛和精神疾病。最终，来自磁电纳米粒子的电场可以用来连接神经元和仿生装置，从而可以远程控制它们的动作电位。本项目将使参与本研究的本科生和研究生通过广泛的现代技术培训、实践实验经验和通过参加会议获得的沟通技巧大大受益，这些将影响他们未来在学术界或工业界的职业生涯。

The goal of this exploratory research is to develop a technique for remote stimulation of mammalian cells using nanoscale electric fields. This new concept takes advantage of magnetoelectric properties of multiferroic nanoparticles which can generate local electric fields in the proximity of cell membranes when subjected to external magnetic field pulses. These fields are expected to control functions of voltage-gated ion channels, which are voltage-sensitive macromolecules, responsible for transport of Na+, K+ ions across cell membranes. To elucidate feasibility of this new approach PI will use computer simulations and thin film technology at the Advanced Materials Research Institute of the University of New Orleans to design and fabricate nanoelectrodes and patterned arrays of multiferroic particles to generate nanoscale electric fields. The response of the ion channels to the nano-electrostimulation will be measured by Co-PI in his Biophysics Laboratory at Loyola University New Orleans using modified patch-clamp technique. Since future in-vivo applications of the new method will involve use of multiferroic nanocomposites of magnetic and ferroelectric nanoparticles, The Co-PI will also devise methods of delivery of the ferroelectric nanoparticles and will determine their toxicity and binding to mammalian cells. This collaborative research will efficiently use resources and expertise in physics, materials science and biophysics available at the University of New Orleans and Loyola University New Orleans. Intellectual Merit: The proposed research is an attempt to utilize magnetoelectric properties of multiferroic nanoparticles as wireless probes to electrostimulate mammalian cells. The effects of external nanoscale electric fields on ion transport in mammalian cells have not been studied and this research will provide better understanding of fundamental functions of the cells. Although there have been extensive studies on applications of magnetic nanoparticles in biological systems, little is known about the interactions of ferroelectric nanoparticles with mammalian cells and proposed research will shed light on feasibility of biomedical applications of ferroelectric materials and their composites. New methods will be developed for intracellular and extracellular delivery of the nanoparticles, and patch-clamp technique will be modified to test responses of the ion-channels in living cells to applied magnetic fields with the frequency up to 5 kHz. The sequences of the pulses, as well as properties of the nanoparticles will be tuned to detetermine control of ion currents. Broader Impacts: The outcome of this research on is expected to have profound effect on several disciplines, such as biology, medicine, biotechnology and bionics. Successful control of ion transport using magnetic field pulses offers alternative noninvasive method to treat ion-channel related diseases, such as cystic fibrosis, diabetes, cardiac arrhythmias, neurologic and psychiatric diseases, gastrointestinal disorders, cardiovascular diseases and hypertension. Since voltage-gated ion channels are responsible for triggering and propagation of action potentials in neurons the new mechanism of stimulation of ion channels can be used to treat pain and psychiatric diseases. Ultimately, electric fields from magnetoelectric nanoparticles can be used to interface neurons with bionic devices which can remotely control their action potentials. This project will greatly benefit undergraduate and graduate students participating in this research through extensive training in modern technologies, hands on experiment experience and communication skills gained through participation in meetings and conferences that will impact their future professional careers in academia or industry.