Research Press Release

Watching single molecules under flow

Nature Methods

February 7, 2011

Methods for improved single-molecule fluorescence experiments are reported in two papers published online this week in Nature Methods. Understanding single molecule dynamics is important on a fundamental level as well as for modeling protein structure and for drug design.

Observing single molecules can yield insights into molecular behaviour that cannot be discerned from typical experiments in which populations of molecules are studied. For example, the intermediate states that a protein briefly occupies as it goes from an unfolded, inactive state to a folded, functional structure, can often only be detected by following a single protein as it folds.

Ashok Deniz and colleagues report a rapid microfluidic mixing device in which the output flow is slowed down such that it is compatible with single-molecule detection. They use the device to study the early folding steps of an intrinsically disordered protein, alpha-synuclein, using a detection technique known as single-molecule fluorescence resonance energy transfer.

In separate work, Devdoot Majumdar and colleagues substantially increase the throughput of single-molecule experiments. Using an automated microfluidic mixing device that is compatible with fluorescence imaging, they monitor single-molecule conformational changes and enzymatic activity under various environmental conditions at a scale that would be inaccessible with manual methods.

DOI:10.1038/nmeth.1568 | Original article

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