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Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12622-7. Epub 2007 May 11.

Principal-components analysis of shape fluctuations of single DNA molecules.

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Department of Chemistry, Stanford University, Stanford, CA 94305, USA.


Thermal fluctuations agitate molecules in solution over a broad range of times and distances. By passively watching the shape fluctuations of a thermally driven biomolecule, one can infer properties of the underlying interactions that determine the motion. We applied this concept to single molecules of fluorescently labeled lambda-DNA, a key model system for polymer physics. In contrast to most other single-molecule DNA experiments, we examined the unstretched, equilibrium state of DNA by using an anti-Brownian electrokinetic trap to confine the center of mass of the DNA without perturbing its internal dynamics. We analyze the long-wavelength conformational normal modes, calculate their spring constants, and measure linear and nonlinear couplings between modes. The modes show strong signs of nonlinear hydrodynamics, a feature of the underlying equations of polymer dynamics that has not previously been reported and is neglected in the widely used Rouse and Zimm approximations.

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