New technology for molecular interactions with the cells

New technology for molecular interactions with the cells

Researchers describe a new method for examining small molecules and their communication with membrane proteins. The research will allow scientists and clinicians to study these interactions at an astonishingly minute scale with unprecedented precision.

The method permits the first direct, real-time measurement of the binding kinetics of small molecules with membrane proteins on intact cells, without the use of molecular labeling.

The study appears in the current issue of the journal Science Advances.

Accurate drug design requires an understanding not only of the small molecule drugs and the membrane proteins they bind to, but information about how the process develops over time -- the so-called binding kinetics of the system. The rates at which drugs bind with and dissociate from receptors have a direct impact on drug efficacy and safety.

The optimization of binding kinetics allows drug designers to precisely control two critical parameters known as Kon and Koff. These represent the small molecule-protein binding event and the dissociation of the small molecule.

The study 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.