The thermodynamics and kinetics of protein folding and protein aggregation in vivo are of great importance in numerous scientific areas including fundamental biophysics research, nanotechnology, and medicine. However, these processes remain poorly understood in both in vivo and in vitro systems. Here we extend an established model for protein aggregation that is based on the kinetic equations for the moments of the polymer size distribution by introducing macromolecular crowding particles into the model using scaled-particle and transition-state theories. The model predicts that the presence of crowders can either speed up, cause no change to, or slow down the progress of the aggregation compared to crowder-free solutions, in striking agreement with experimental results from nine different amyloid-forming proteins that utilized dextran as the crowder. These different dynamic effects of macromolecular crowding can be understood in terms of the change of excluded volume associated with each reaction step.

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研究分子拥挤对蛋白质聚集动力学的影响

体内蛋白质折叠和蛋白质聚集的热力学和动力学在许多科学领域都非常重要，包括基础生物物理学研究，纳米技术和医学。但是，这些过程在体内和体外系统中仍然知之甚少。在这里，我们通过使用比例粒子和过渡态理论将高分子拥挤粒子引入模型，从而扩展了基于聚合物尺寸分布瞬间动力学方程的蛋白质聚集模型。该模型预测，与无拥挤的解决方案相比，拥挤的存在会加快聚合速度，不引起更改或减慢聚合进度，与使用葡聚糖作为拥挤物的9种不同淀粉样蛋白形成蛋白的实验结果惊人地吻合。可以根据与每个反应步骤相关的排除体积的变化来理解大分子拥挤的这些不同的动力学效应。