Transverse Dynamic Force Spectroscopy - ACS Publications

microscopy (AFM) and optical tweezers have enabled the force-extension response of single ... development of single molecule dynamic force spectroscop...
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Langmuir 2002, 18, 1729-1733

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Transverse Dynamic Force Spectroscopy: A Novel Approach to Determining the Complex Stiffness of a Single Molecule A. D. L. Humphris,* M. Antognozzi, T. J. McMaster, and M. J. Miles H. H. Wills Physics Laboratory, University of Bristol, Tyndall Avenue, Bristol, BS8 1TL, United Kingdom Received August 16, 2001. In Final Form: November 14, 2001 Piconewton force sensitivity and angstrom position control offered by instruments such as atomic force microscopy (AFM) and optical tweezers have enabled the force-extension response of single molecules to be investigated. However, to fully investigate the dynamic and energetic properties of a single molecule, it is necessary to detect both conservative (elastic) and dissipative (viscous) components of the extension response. We present a transverse dynamic force microscope (TDFM) capable of measuring this complex quantity. This new force spectroscopy technique offers true control over the tip-surface distance revealing information not accessible by conventional dc atomic force spectroscopy. Results are presented for the force extension response of a single polysaccharide molecule. To the authors knowledge, this is the first time the complex mechanical properties of a single polymer molecule have been measured by TDFM. These observations are in agreement with previous dynamic AFM experiments.

Introduction The development of new instruments with piconewton force sensitivity and angstrom displacement control have enabled the study of the mechanical properties of single molecules.1-5 These experiments have given new insight not only into intra- and intermolecular forces but also into protein folding5,6 and conformational transitions of polymers.2,7 However the most commonly used techniques, conventional atomic force microscopy (AFM) and optical tweeters, are only capable of measuring static forces and are not able, therefore, to investigate and address the molecular viscoelastic behavior. In this paper we present a system based on a transverse dynamic force microscope8 (TDFM) and demonstrate how extra information describing the dynamic, viscoelastic properties of the molecule can be accessed. In TDFM (more commonly known as shear force microscopy) a cylindrical probe is mounted perpendicularly to the sample and set into transverse oscillation. The main limitation for the development of single molecule dynamic force spectroscopy using AFM and optical tweezers has been the low quality factor of the commonly used force transducers in liquid environments. For example a conventional AFM cantilever has a quality factor of the order of 1 and optical tweezers