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Force Spectra and Optical Measurements of Single Ligand-Receptor Pairs

William F. Heinz*, Kenneth D. Weston, Bertrand Navarro, Pernelle Bernardi, Lori S. Goldner

Optical Technology Division, National Institute of Standards and Technology,
Gaithersburg, MD 20899-8442 USA

This is an abstract for a presentation given at the
Eighth Foresight Conference on Molecular Nanotechnology.
There will be a link from here to the full article when it is available on the web.


The interactions between biological macromolecules and macromolecular assemblies are central to the proper functioning of biological systems. Historically, these interactions have been measured by techniques that measure the averaged interactions of large ensembles of particles. Recently, a number of experimental approaches have been developed that enable the study of single molecules.1,2,3,4 Two advantages that single molecule experiments have over average measurements on ensembles are (1) the distributions that make up the average and the heterogeneity of the population can be determined and (2) the time-dependent behavior of molecules can be measured, whether they are in equilibrium, non-equilibrium, or undergoing some kind of reaction. Both types of information are masked by the average measurement. Understanding interactions on the level of single molecules provides framework for the design of new drugs, treatments for disease, and forms a basis for using those molecules as building blocks for new devices.

Interactions between individual molecules depend on many variables including orientation, conformation, local environment, and separation distance. Two single molecule techniques, atomic force microscopy and single-molecule fluorescence spectroscopy, are sensitive to those parameters. Specifically, the atomic force microscope5 (AFM) is a tool for measuring forces between nanometer-scale objects in physiological conditions (i.e.: in aqueous solutions) and has been used to measure interactions between individual biomolecules.6 Single-molecule fluorescence resonant energy transfer7 (sm-FRET) and fluorescence polarization spectroscopy8 (FPS) are sensitive to the conformation, orientation, and dynamics of individual molecules.1 The combination of an AFM with sm-FRET and FPS measurements provides a more complete description of the interaction between single molecules, the effects of molecular orientation and conformation on the interaction forces (and vice versa) as a function of separation distance.

Here we report on progress towards the simultaneous measurement of force and orientational and conformational dynamics of a single ligand-receptor pair during the binding and unbinding process in aqueous conditions.

1 Bai, C., C. Wang, X. S. Xie, and P. G. Wolynes. 1999. PNAS 96:11075-11076.
2 Gimzewski, J. K. and C. Joachim. 1999. Science. 283:1683-1688.
3 Mehta, A. D., M. Rief, J. A. Spudich, D. A. Smith, and R. M. Simmons. 1999. Science. 283:1689-1695.
4 Weiss, S. 1999. Science. 283:1676-1683.
5 Binnig, G., C. F. Quate, and C. Gerber. 1986. Phys. Rev. Lett. 56:930-933.
6 Heinz, W. F., and J. H. Hoh. 1999. Trends Biotechnol. 17:143-150.
7 Ha, T., T. Enderle, D. F. Ogletree, D. S. Chemla, P. R. Selvin, and S. Weiss. 1996. PNAS. 93:6264-6268.
8 Ha, T., T. A. Laurence, D. S. Chemla, and S. Weiss. 1999. JPCB. 103:6839-6850.

*Corresponding Address:
William F. Heinz
Optical Technology Division, National Institute of Standards and Technology
100 Bureau Dr. Mail Stop 8442
Gaithersburg, MD 20899-8442 USA


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