Force-Induced Conformational Transitions in Single Polysaccharide Molecules by AFM

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MARSZALEK MCB9808310 Polysaccharide molecules have been found to behave as entropic springs with complex force-dependent elasticity. Polysaccharides can adopt a variety of secondary structures in solution due to different types of monomers and glycosidic linkages between the monomers (e.g. alpha-(1-4), beta (1-4), alpha-(1-6), etc.). This study examines the hypothesis that the elasticity of polysaccharides is related to their secondary structures, and seeks to identify force-induced conformational transitions that may abruptly affect the length and elasticity of these molecules. Towards these aims a representative group of linear polysaccharides that tend to adopt distinct secondary structures - extended and ribbon-like cellulosic chains, wide helical amylosic chains, and flexible dextran-like chains - will be investigated by stretching single molecules vertically in the atomic force microscope. Different derivatives of polysaccharides will be used to study how the steric and electrostatic effects of the substituted groups affects chain elasticity. The kinetics of the force-induced conformational transitions (continuous or discontinuous) will be probed by varying the rate at which extension of the molecule and the elastic force is generated. Molecular dynamics (MD) simulations of disaccharide segments will be carried out to investigate how an external mechanical force affects geometry of covalent bonds and conformations of the glucopyranose ring. This will help to identify the mechanism underlying enthalpic elasticity and possible force-induced conformational transitions. Information derived from the AFM experiments and MD calculations will be integrated to construct a kinetic model, using Monte Carlo simulation, of polysaccharide elasticity that will reproduce force-extension characteristics. The elastic and viscoelastic properties of polysaccharides are widely exploited in nature and they have many industrial applications. The proposed studies will generate valuable inform ation on the atomic basis of polysaccharide elasticity. In addition, deciphering the nature of conformational transitions in stretched polysaccharides may shed light on the mechanisms of force-induced transitions in more complex macromolecules, such as DNA.