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使用纳米级电场远程刺激哺乳动物细胞的技术。这一新概念利用了多铁纳米粒子的磁电性质，当受到外加磁场脉冲时，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，这些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将使用计算机模拟和新奥尔良大学先进材料研究所的薄膜技术来设计和制造纳米电极和多铁性粒子的图案化阵列，以产生纳米级电场。Co-PI将在他位于新奥尔良罗约拉大学的生物物理实验室使用改进的膜片钳技术测量离子通道对纳米电刺激的响应。由于未来新方法的体内应用将涉及使用磁性和铁电纳米颗粒的多铁纳米复合材料，Co-PI还将设计铁电纳米颗粒的输送方法，并将确定它们的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新奥尔良洛约拉大学在物理、材料科学和生物物理学方面的资源和专业知识。智能优点：这项拟议的研究是一项尝试，利用多铁纳米颗粒的磁电特性作为无线探测器来电刺激哺乳动物细胞。外界纳米尺度电场对哺乳动物细胞内离子传输的影响尚未被研究，这项研究将为更好地理解细胞的基本功能提供帮助。虽然磁性纳米颗粒在生物系统中的应用已经有了广泛的研究，但对铁电纳米颗粒与哺乳动物细胞的相互作用知之甚少，所提出的研究将有助于揭示铁电材料及其复合材料在生物医学应用的可行性。将开发细胞内和细胞外传递纳米颗粒的新方法，并将改进膜片钳技术，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。脉冲的顺序以及纳米颗粒的性质将被调整，以确定离子电流的控制。更广泛的影响：这项研究的结果预计将对生物学、医学、生物技术和仿生学等几个学科产生深远影响。利用磁场脉冲成功地控制离子转运，为治疗囊性纤维化、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等离子通道相关疾病提供了替代的非侵入性方法。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，磁电纳米颗粒产生的电场可以用来连接神经元和仿生设备，这些仿生设备可以远程控制神经元的动作电位。该项目将使参与这项研究的本科生和研究生通过广泛的现代技术培训、动手实验经验和通过参加会议获得的沟通技能大大受益，这些会议和会议将影响他们未来在学术界或行业的职业生涯。

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.