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Science 315 (5809): 233-237

Copyright © 2007 by the American Association for the Advancement of Science

A Systems Approach to Measuring the Binding Energy Landscapes of Transcription Factors

Sebastian J. Maerkl1,2, and Stephen R. Quake2*

Abstract: A major goal of systems biology is to predict the function of biological networks. Although network topologies have been successfully determined in many cases, the quantitative parameters governing these networks generally have not. Measuring affinities of molecular interactions in high-throughput format remains problematic, especially for transient and low-affinity interactions. We describe a high-throughput microfluidic platform that measures such properties on the basis of mechanical trapping of molecular interactions. With this platform we characterized DNA binding energy landscapes for four eukaryotic transcription factors; these landscapes were used to test basic assumptions about transcription factor binding and to predict their in vivo function.

1 Biochemistry and Molecular Biophysics Option, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
2 Department of Bioengineering, Stanford University and Howard Hughes Medical Institute, 318 Campus Drive, Stanford, CA 94305, USA.

* To whom correspondence should be addressed. E-mail: quake{at}stanford.edu

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