具有三种状态的热力学一致的跨桥模型用于肌肉收缩
Thermodynamically Consistent Modeling of ATP-Driven Cross-Bridge Dynamics in Muscle Contraction
AI总结：
本文提出了一种具有三种状态的热力学一致跨桥模型，用于描述肌肉收缩，结合Hill循环和Huxley滑动丝机制，通过能量变分方法统一框架，展示ATP水解对力-速度关系的影响。
摘要：
肌肉收缩是一种典型的多尺度化学机械过程，在分子层面的ATP水解驱动着更大尺度上的力生成和机械工作。长期以来的挑战是将微观的跨桥动力学与宏观可观察量连接起来，同时保持一个明确的、热力学一致的能量预算，用于化学到机械转换。在这里，我们使用能量变分方法（EnVarA）将Hill的循环-亲和观点与Huxley的滑动丝机制统一在一个热力学封闭框架内。我们为跨桥种群制定了一个三态福克-计划跳描述，这些种群在状态依赖的自由能景观上演变，在其中ATP水解通过局部详尽平衡进入，并偏转过渡率。丝滑动速度被纳入福克-计划动态的对流传输机制中，因此机械功率与外部运动的交换从由此产生的能量耗散定律以及化学输入和不可逆耗散中显式出现。在化学稳态条件和快速平衡闭合对于附着亚状态的情况下，该模型减少为一个封闭的二态分子马达描述；在进一步的奇异极限下，这种减少恢复为Huxley型的传输-反应方程。概念验证模拟的简化模型重现了Hill-like的力-速度关系，并展示了ATP可用性如何调节力-速度曲线，同时保持其特征Hill型形状。
英文摘要：
Muscle contraction is a prototypical multiscale chemomechanical process in which ATP hydrolysis at the molecular level drives force generation and mechanical work at larger scales. A central challenge is to incorporate the free energy supplied by ATP hydrolysis into a mechanical cross-bridge model in a way that is thermodynamically consistent and connects microscopic motor cycling to macroscopic force generation. Here we use the Energetic Variational Approach (EnVarA) to combine Hill's cycle-affinity viewpoint with Huxley's sliding-filament mechanics in a single thermodynamically consistent framework. We formulate a three-state Fokker--Planck--jump description for cross-bridge densities evolving on state-dependent free-energy landscapes, and treat ATP, ADP, and Pi as reacting and diffusing chemical species that share the same free-energy functional as the cross-bridge densities. ATP hydrolysis enters the model through local detailed balance, which biases the transition rates. Filament sliding velocity is incorporated as a convective transport term in the Fokker--Planck dynamics, so mechanical power output is defined directly from the energy balance law. Under chemostatted conditions and a fast-equilibration assumption for the two attached states, the model reduces to a closed two-state molecular motor description; in a further small-diffusion limit, this reduction recovers a Huxley-type transport-reaction equation whose effective attachment and detachment rates are derived from the underlying three-state cycle rather than prescribed phenomenologically, with their strain, ATP, and phosphate dependence fixed by the energy landscapes and local detailed balance. We calibrate the reduced model against cross-bridge-level observables and show that it reproduces key velocity-dependent trends and yields a Hill-like force--velocity relation comparable to established cross-bridge models.
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