This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gerland, U. Articles by Hwa, T. Search for Related Content PubMed PubMed Citation Articles by Gerland, U. Articles by Hwa, T.

Mechanically Probing the Folding Pathway of Single RNA Molecules

Ulrich Gerland ^*, Ralf Bundschuh  and Terence Hwa ^*

^* Department of Physics, University of California at San Diego, La Jolla, California 92093-0319; and Department of Physics, The Ohio State University, Columbus, Ohio 43210-1106

Correspondence: Address reprint requests to Ulrich Gerland, 9500 Gilman Dr., La Jolla, CA 92093 USA. Tel.: 858-534-7256; Fax: 858-534-7697; E-mail: gerland{at}physics.ucsd.edu.

We study theoretically the denaturation of single RNA molecules by mechanical stretching, focusing on signatures of the (un)folding pathway in molecular fluctuations. Our model describes the interactions between nucleotides by incorporating the experimentally determined free energy rules for RNA secondary structure, whereas exterior single-stranded regions are modeled as freely jointed chains. For exemplary RNA sequences (hairpins and the Tetrahymena thermophila group I intron), we compute the quasiequilibrium fluctuations in the end-to-end distance as the molecule is unfolded by pulling on opposite ends. Unlike the average quasiequilibrium force-extension curves, these fluctuations reveal clear signatures from the unfolding of individual structural elements. We find that the resolution of these signatures depends on the spring constant of the force-measuring device, with an optimal value intermediate between very rigid and very soft. We compare and relate our results to recent experiments by Liphardt et al. (2001).

This article has been cited by other articles:

				C. Hyeon and D. Thirumalai Mechanical Unfolding of RNA: From Hairpins to Structures with Internal Multiloops Biophys. J., February 1, 2007; 92(3): 731 - 743. [Abstract] [Full Text] [PDF]

				N. W. Moore and T. L. Kuhl The Role of Flexible Tethers in Multiple Ligand-Receptor Bond Formation between Curved Surfaces Biophys. J., September 1, 2006; 91(5): 1675 - 1687. [Abstract] [Full Text] [PDF]

				C. Hyeon and D. Thirumalai Forced-Unfolding and Force-Quench Refolding of RNA Hairpins Biophys. J., May 15, 2006; 90(10): 3410 - 3427. [Abstract] [Full Text] [PDF]

				K. A. Walther, J. Brujic, H. Li, and J. M. Fernandez Sub-Angstrom Conformational Changes of a Single Molecule Captured by AFM Variance Analysis Biophys. J., May 15, 2006; 90(10): 3806 - 3812. [Abstract] [Full Text] [PDF]

				F. Liu, H. Tong, and Z.-c. Ou-Yang Force Unfolding Single RNAs Biophys. J., March 15, 2006; 90(6): 1895 - 1902. [Abstract] [Full Text] [PDF]

				M. Andersson, E. Fallman, B. E. Uhlin, and O. Axner A Sticky Chain Model of the Elongation and Unfolding of Escherichia coli P Pili under Stress Biophys. J., March 1, 2006; 90(5): 1521 - 1534. [Abstract] [Full Text] [PDF]

				C. Hyeon and D. Thirumalai Chemical Theory and Computation Special Feature: Mechanical unfolding of RNA hairpins PNAS, May 10, 2005; 102(19): 6789 - 6794. [Abstract] [Full Text] [PDF]

				M. Manosas and F. Ritort Thermodynamic and Kinetic Aspects of RNA Pulling Experiments Biophys. J., May 1, 2005; 88(5): 3224 - 3242. [Abstract] [Full Text] [PDF]

				F. Liu and Z.-c. Ou-Yang Monte Carlo Simulation for Single RNA Unfolding by Force Biophys. J., January 1, 2005; 88(1): 76 - 84. [Abstract] [Full Text] [PDF]