论文标题
体内测量的机理,缩放和蛋白质聚集速率
Mechanism, scaling and rates of protein aggregation from in vivo measurements
论文作者
论文摘要
蛋白质聚集体的形成和增殖在许多毁灭性神经脱生性疾病中起着核心作用。许多实验研究表明,现有骨料复制的能力是在各种疾病中产生其致病作用的关键特性。但是,鉴于体内过程的复杂性,目前尚无原则性的一般方法来获得基于生命系统测量结果构成的基本步骤的速率。为了应对这一挑战,在这里我们提出了一种一般方法,用于分析聚集动力学,该动力学考虑了广泛的流程,这些过程可以由缩放解决方案系列描述。我们的方法不仅限于原纤维聚集体,而且适用于任何骨料形状。我们表明,即使是从生命系统中的实验数据中拟合简单的逻辑函数,也可以可靠地提取速率,并提供非常通用的分析表达,将指数速率与单体浓度的缩放与基础反应的显微镜细节相关联。因此,该方法可用于推断从复杂系统中的宏观测量中驱动聚集过程的微观机制。
The formation and proliferation of protein aggregates play a central role in a number of devastating neuro-degenerative diseases. Many experimental studies indicate that the ability of existing aggregates to replicate is a key property in generating their pathogenic effect across a range of diseases. However, given the complexity of the process in vivo, no principled general approach currently exists to obtain the rates of the fundamental steps that underlie aggregate formation from measurements in living systems. In order to address this challenge, here we present a general approach for analysing aggregation kinetics that considers broad classes of processes that can be described by a family of scaling solutions. Our approach is not limited only to fibrillar aggregates, but applies to any aggregate shape. We show that the rates can reliably be extracted by fitting of a simple logistic function, even from experimental data in living systems, and give a very general analytical expression that relates the scaling of the exponential rate with monomer concentration to the microscopic details of the underlying reaction. This approach can thus be used to infer the microscopic mechanism driving the aggregation process from macroscopic measurements in complex systems.