Research ArticleBIOTECHNOLOGY

Kinetics of small molecule interactions with membrane proteins in single cells measured with mechanical amplification

Science Advances  23 Oct 2015:
Vol. 1, no. 9, e1500633
DOI: 10.1126/sciadv.1500633

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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.

Keywords
  • small molecule–membrane protein interaction in situ measurement
  • single cell
  • label-free detection
  • kinetics measurement
  • optical imaging
  • mechanical amplification

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

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