Force-Induced Conformational Transitions in Single Polysaccharide Molecules by AFM

Marszalek MCB9808310多糖分子被发现表现为具有复杂的力相关弹性的熵弹簧。由于不同类型的单体和单体之间的糖苷键(如α-(1-4)、β(1-4)、α-(1-6)等)，多糖在溶液中可以采用不同的二级结构。这项研究检验了多糖的弹性与其二级结构有关的假设，并试图识别可能突然影响这些分子的长度和弹性的力诱导构象转变。为了达到这些目标，将通过在原子力显微镜中垂直拉伸单分子来研究一组具有代表性的线性多糖，它们倾向于采用不同的二级结构-延长的和带状的纤维素链、宽的螺旋淀粉链和柔性的葡聚糖链。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。力诱导构象转变(连续或不连续)的动力学将通过改变分子伸展和弹性力的产生速度来探讨。二糖链段的分子动力学(MD)模拟将被用来研究外力如何影响共价键的几何形状和葡萄糖环的构象。这将有助于确定焓弹性和可能的力诱导构象转变的机制。从AFM实验和MD计算中获得的信息将被整合在一起，使用蒙特卡罗模拟来构建一个多糖弹性的动力学模型，该模型将再现力-拉伸特性。多糖的弹性和粘弹性性质在自然界中得到了广泛的开发，并具有许多工业应用。建议的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本质可能有助于揭示更复杂的大分子，如DNA中的力诱导转变的机制。

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.