The Problem with Inventing Molecular Mechanisms to Fit Thermodynamic Equations of Muscle.
The Problem with Inventing Molecular Mechanisms to Fit Thermodynamic Equations of Muscle.
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DOI：
10.3390/ijms242015439
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发表时间：
2023-10-22
影响因子：
5.6
通讯作者：
Baker J
中科院分区：
文献类型：
--
作者：
Baker J
迄今为止，文献中几乎所有的肌肉收缩模型都是分子动力冲程模型，尽管这种微粒机制遭到了几个世纪以来科学界的反对，85年来无可辩驳的证据表明肌肉是一个热力学系统，并且通过四分之一个世纪的直接观察表明肌肉收缩的分子机制是分子开关，而不是分子动力冲程。分子开关的集合是一个二元机械热力学系统，A.V.直接导出 Hill 的肌肉力-速度关系，其中 Hill 的参数 a 是无负载肌肉缩短时所承受的内力，Hill 的参数 b 是开关位移 d 和肌动蛋白-肌球蛋白 ATP 酶速率的乘积。忽略这个模型和之前几个世纪的热力学，微粒学家继续开发分子动力冲程模型，为希尔的 a 和 b 参数添加了他们 65 年的“新”、“创新”和“非常规”分子机制，其中没有一个与潜在的物理化学相似。值得注意的是，微粒学界要求热力学学家来解释这些差异，正如本文所概述的，我已经这样做了 25 年。微粒学家早就应该对他们的机制负责，因为从各方面来看，这些机制都没有科学基础。赌注很高。分子动力冲程模型广泛应用于研究和临床决策中，半个多世纪以来，它混淆了我们对地球上最高效、最清洁的燃烧机器之一的内部工作原理的理解。微粒学家将这些模型作为科学呈现给利益相关者是有问题的，而事实上微粒学家几十年来一直在积极捍卫这些模型以对抗科学。科学家们前进的道路是停止对肌肉热力学毫无根据的拒绝，并开始测试红细胞和热力学机制，目的是反驳这些假设中的一个或另一个。
Almost every model of muscle contraction in the literature to date is a molecular power stroke model, even though this corpuscular mechanism is opposed by centuries of science, by 85 years of unrefuted evidence that muscle is a thermodynamic system, and by a quarter century of direct observations that the molecular mechanism of muscle contraction is a molecular switch, not a molecular power stroke. An ensemble of molecular switches is a binary mechanical thermodynamic system from which A.V. Hill’s muscle force–velocity relationship is directly derived, where Hill’s parameter a is the internal force against which unloaded muscle shortens, and Hill’s parameter b is the product of the switch displacement, d, and the actin–myosin ATPase rate. Ignoring this model and the centuries of thermodynamics that preceded it, corpuscularians continue to develop molecular power stroke models, adding to their 65-year jumble of “new”, “innovative”, and “unconventional” molecular mechanisms for Hill’s a and b parameters, none of which resemble the underlying physical chemistry. Remarkably, the corpuscularian community holds the thermodynamicist to account for these discrepancies, which, as outlined here, I have done for 25 years. It is long past time for corpuscularians to be held accountable for their mechanisms, which by all accounts have no foundation in science. The stakes are high. Molecular power stroke models are widely used in research and in clinical decision-making and have, for over half a century, muddied our understanding of the inner workings of one of the most efficient and clean-burning machines on the planet. It is problematic that corpuscularians present these models to stakeholders as science when in fact corpuscularians have been actively defending these models against science for decades. The path forward for scientists is to stop baseless rejections of muscle thermodynamics and to begin testing corpuscular and thermodynamic mechanisms with the goal of disproving one or the other of these hypotheses.
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影响因子：
4.6
作者：
Baker, Josh E.
通讯作者：
Baker, Josh E.
影响因子：
5.6
作者：
Pertici, Irene;Bongini, Lorenzo;Caremani, Marco;Reconditi, Massimo;Linari, Marco;Piazzesi, Gabriella;Lombardi, Vincenzo;Bianco, Pasquale
通讯作者：
Bianco, Pasquale
影响因子：
3.4
作者：
Baker, Josh E.
通讯作者：
Baker, Josh E.
影响因子：
3.4
作者：
Baker, JE;Brosseau, C;Warshaw, DM
通讯作者：
Warshaw, DM
影响因子：
4.8
作者：
Haldeman, Brian D.;Brizendine, Richard K.;Cremo, Christine R.
通讯作者：
Cremo, Christine R.