Force-Induced Conformational Transitions in Single Polysaccharide Molecules by AFM

MARSZALEK MCB 9808310 已经发现多糖分子表现为具有复杂的力依赖弹性的熵弹簧。 由于不同类型的单体和单体之间的糖苷键（例如α-（1-4）、β（1- 4）、α-（1-6）等），多糖在溶液中可以采用多种二级结构。 本研究探讨了多糖的弹性与其二级结构有关的假设，并试图确定力诱导的构象转变，可能会突然影响这些分子的长度和弹性。 为了实现这些目标，一组代表性的线性多糖，往往采取不同的二级结构-延长和带状纤维素链，宽螺旋淀粉链，和灵活的葡聚糖样链-将通过拉伸单分子在原子力显微镜垂直调查。 不同的多糖衍生物将被用来研究取代基团的空间和静电效应如何影响链弹性。 力诱导的构象转变（连续或不连续）的动力学将通过改变分子的延伸和弹性力产生的速率来探测。 分子动力学（MD）模拟二糖片段将进行调查如何影响外部机械力的共价键的几何形状和构象的吡喃葡萄糖环。 这将有助于确定潜在的弹性和可能的力诱导的构象转变的机制。 来自AFM实验和MD计算的信息将被整合到构建一个动力学模型，使用Monte Carlo模拟，多糖的弹性，将重现力的延伸特性。 多糖的弹性和粘弹性性质在自然界中被广泛利用，并且它们具有许多工业应用。 这些研究将在多糖弹性的原子基础上产生有价值的信息。 此外，破译拉伸多糖中构象转变的性质可能会揭示更复杂的大分子（如DNA）中力诱导转变的机制。

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.