title: Kinetics of small molecule interactions with membrane proteins in single cells measured with mechanical amplification.
abstract: Measuring small molecule interactions with membrane proteins in single cells is critical for understanding many cellular processes and for screening drugs. However, developing such a capability has been a difficult challenge. We show that molecular interactions with membrane proteins induce a mechanical deformation in the cellular membrane, and real-time monitoring of the deformation with subnanometer resolution allows quantitative analysis of small molecule-membrane protein interaction kinetics in single cells. This new strategy provides mechanical amplification of small binding signals, making it possible to detect small molecule interactions with membrane proteins. This capability, together with spatial resolution, also allows the study of the heterogeneous nature of cells by analyzing the interaction kinetics variability between different cells and between different regions of a single cell.
authors.affiliation: Center for Bioelectronics and Biosensors, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA. ; School of Electrical Computer and Energy Engineering, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Center for Bioelectronics and Biosensors, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Shan
authors.affiliation: Center for Bioelectronics and Biosensors, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA. ; School of Electrical Computer and Energy Engineering, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Fenni
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Center for Bioelectronics and Biosensors, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Shaopeng
authors.initials: S
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.
authors.forename: Hong-Yuan
authors.initials: HY
authors.lastname: Chen
authors.affiliation: Center for Bioelectronics and Biosensors, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA. ; School of Electrical Computer and Energy Engineering, Arizona State University, Tempe, AZ 85287, USA. ; State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.
authors.forename: Nongjian
authors.initials: N
authors.lastname: Tao
keywords: kinetics measurement; label-free detection; mechanical amplification; optical imaging; single cell; small molecule–membrane protein interaction in situ measurement