Electrical activities in cells play key roles in many important biological processes, including brain signal pro- cessing, cardiac functions, wound healing and other developmental processes. Currently, the most widely used experimental tool for studying the cellular electrical activities measures a local electrical current or voltage with a microelectrode or micropipette. While sensitive, it lacks spatial resolution and can be invasive. Developing a non-invasive and sensitive technology that can image small electrical signals in cells with high spatial and tem- poral resolutions has been a long-standing goal. This renewal project develops a plasmonic-based electrical impedance microscope (P-EIM) for label-free imaging of electrical signals in cells. The microscope converts an electrical signal to a plasmonic signal, which is imaged optically. Building on the success of substantial prelimi- nary studies, the PI propose to develop a new capability of P-EIM for studying cellular electrical activities, vali- date its performance using reference technologies, and establish key applications, including imaging action potential propagations in neurons, drug induced ion channel activity changes, and potential distributions in cells during wound healing processes. The success of this project will lead to a new tool for studying electrical activities in cells with temporal and spatial resolutions that are not possible with the existing technologies. This new label-free imaging tool will provide new insights into the roles of electrical activities in biological processes, and a new method for screening drugs targeting neuronal and cardiac functions, wound healing and other de- velopmental processes.

Public Health Relevance

This project develops a label-free imaging technology for studying electrical activities in cells with high spatial and temporal resolutions. This unique capability will provide new insights into the roles of electrical activities in many biological processes, including brain and cardiac functions, wound healing and tissue development, and will lead to a new method for screening drugs targeting these processes.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM107165-07
Application #
10001533
Study Section
Cellular and Molecular Technologies Study Section (CMT)
Program Officer
Sammak, Paul J
Project Start
2014-07-01
Project End
2022-08-31
Budget Start
2020-09-01
Budget End
2021-08-31
Support Year
7
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Arizona State University-Tempe Campus
Department
Miscellaneous
Type
Organized Research Units
DUNS #
943360412
City
Tempe
State
AZ
Country
United States
Zip Code
85287
Yang, Yunze; Liu, Xian-Wei; Wang, Hui et al. (2018) Imaging Action Potential in Single Mammalian Neurons by Tracking the Accompanying Sub-Nanometer Mechanical Motion. ACS Nano 12:4186-4193
Zhang, Fenni; Jing, Wenwen; Hunt, Ashley et al. (2018) Label-Free Quantification of Small-Molecule Binding to Membrane Proteins on Single Cells by Tracking Nanometer-Scale Cellular Membrane Deformation. ACS Nano 12:2056-2064
Ma, Guangzhong; Syu, Guan-Da; Shan, Xiaonan et al. (2018) Measuring Ligand Binding Kinetics to Membrane Proteins Using Virion Nano-oscillators. J Am Chem Soc 140:11495-11501
Wang, Yixian; Shan, Xiaonan; Wang, Shaopeng et al. (2016) Imaging Local Electric Field Distribution by Plasmonic Impedance Microscopy. Anal Chem 88:1547-52
Lu, Jin; Yang, Yunze; Wang, Wei et al. (2016) Label-Free Imaging of Histamine Mediated G Protein-Coupled Receptors Activation in Live Cells. Anal Chem 88:11498-11503
Yin, Linliang; Yang, Yunze; Wang, Shaopeng et al. (2015) Measuring Binding Kinetics of Antibody-Conjugated Gold Nanoparticles with Intact Cells. Small 11:3782-8
Zhang, Fenni; Wang, Shaopeng; Yin, Linliang et al. (2015) Quantification of epidermal growth factor receptor expression level and binding kinetics on cell surfaces by surface plasmon resonance imaging. Anal Chem 87:9960-5
Yin, Linliang; Wang, Wei; Wang, Shaopeng et al. (2015) How does fluorescent labeling affect the binding kinetics of proteins with intact cells? Biosens Bioelectron 66:412-6
Wang, Wei; Yin, Linliang; Gonzalez-Malerva, Laura et al. (2014) In situ drug-receptor binding kinetics in single cells: a quantitative label-free study of anti-tumor drug resistance. Sci Rep 4:6609