分子马达与轨道异质集合中随机力谱的力学-动力学参数逆向工程

中文摘要 AI 辅助

分子马达与其轨道相互作用的收缩系统中的异质性在众多细胞生理和病理过程中起着关键作用。然而，其效应无法被假设所有马达具有相同力学-动力学特性的理论模型所捕捉。我们开发了一个随机框架来描述由两个具有不同力学-动力学特性的群体组成的肌球蛋白马达异质集合。假设马达作为独立的力发生器与肌动蛋白丝（其轨道）相互作用，我们推导了等长力的概率分布，并刻画了有限尺寸力涨落的统计特性。所提出的框架包括一个估计程序，该程序同时推断力学-动力学参数和马达集合的大小，从而无需事先规定集合大小。针对合成数据和实验数据的验证表明，该模型能准确捕捉力涨落，并提供对集合大小的现实估计。此外，该框架能够对集合异质性进行定量评估，并推断未知马达物种的特性。该方法为表征异质性肌动蛋白-肌球蛋白系统提供了定量工具，例如由心脏和骨骼肌中不同蛋白亚型的共存，或由突变衍生或工程化变体部分替代天然蛋白所产生的系统。

英文摘要

Heterogeneity in contractile systems of molecular motors interacting with their tracks plays a key role in numerous cellular physiological and pathological processes. However, its effects cannot be captured by theoretical models assuming identical mechano-kinetic properties for all motors. We developed a stochastic framework to describe heterogeneous ensembles of myosin motors comprising two populations with distinct mechano-kinetic properties. Assuming that motors interact with the actin filament (their track) as independent force generators, we derived the probability distribution of the isometric force and characterised the statistics of finite-size force fluctuations. The proposed framework includes an estimation procedure that simultaneously infers the mechano-kinetic parameters and the size of the motor ensemble, eliminating the need to prescribe it a priori. Validation against synthetic and experimental data shows the model accurately captures force fluctuations and provides realistic estimates of the ensemble size. Furthermore, the framework enables a quantitative assessment of ensemble heterogeneity and the inference of an unknown motor species properties. This approach provides a quantitative tool for characterising heterogeneous actin-myosin systems, such as those arising from the co-presence of different protein isoforms in cardiac and skeletal muscle, or from the partial replacement of native proteins with mutation-derived or engineered variants.

发表机构

• Istituto Nazionale di Ottica, Consiglio Nazionale delle Ricerche (CNR-INO)（意大利国家光学研究所，意大利国家研究委员会）
• University of Florence（佛罗伦萨大学）
• Department of Physics and Astronomy, University of Florence（佛罗伦萨大学物理与天文学系）

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