结构生物学sturcture biology explore-8.pdfVIP

? 2000 Nature America Inc. ? review Stretching single molecules into novel conformations using the atomic force microscope Thomas E. Fisher, Piotr E. Marszalek and Julio M. Fernandez A dense network of interconnected proteins and carbohydrates forms the complex mechanical scaffold of living tissues. The recently developed technique of single molecule force spectroscopy using the atomic force microscope (AFM) has enabled a detailed analysis of the force-induced conformations of these molecules and the determinants of their mechanical stability. These studies provide some of the basic knowledge required to understand the mechanical interactions that define all biological organisms. Mechanical stretching in vivo is thought to regulate the function conformational changes in the regulation of physiological func- of proteins, polysaccharides and DNA1–6. The application of tion. This review will focus mostly on the use of the AFM to .com mechanical force to biological polymers produces conforma- study the dynamic changes that proteins undergo in response to tions that are different than those that have been investigated by mechanical force. chemical or thermal denaturation7 and are inaccessible to con- ventional methods of measurement such as NMR spectroscopy The force spectroscopy mode of the AFM and X-ray crystallography. Force-induced conformational tran- In the force-measuring mode of the AFM, single molecules or pairs sitions may therefore be physiologically relevant, and may offer of interacting molecules are stretched between the tip of a micro- novel perspectives on the structure of biomolecules. Recent scopic cantilever and a flat, gold-covered substrate whose position developments in single molecule force spectrosco