Reply to Farrell: Experimental evidence is the ultimate judge for model assumptions.
Reply to Farrell: Experimental evidence is the ultimate judge for model assumptions.
复制标题
回复法雷尔：实验证据是模型假设的最终判断。
DOI：
10.1073/pnas.2017702117
复制
发表时间：
2020
影响因子：
11.1
通讯作者：
Palanker,Daniel
中科院分区：
文献类型：
--
作者：
Ling,Tong;Boyle,KevinC;Palanker,Daniel
在PNAS(1)中，我们报道了在动作电位过程中神经元变形动力学的全场干涉成像。我们描述的成像方法提供了一种非侵入性的方法来观察神经信号，并允许科学家验证他们的模型，与以前的单点测量相比，变形的空间分布提供了更多的自由度。我们还表明，张氏等人提出的基于电压依赖膜张力的力学模型与我们的观察结果相吻合。Farrell(3)认为膜张力应该以抛物线的方式随跨膜电压变化，其最大值在16 mV，正如他们的模型(4)所建议的那样。然而，我们所知道的所有与电压相关的细胞变形的实验测量表明，膜张力与跨膜电压之间存在准线性关系：1)图1c。2)用膜片钳控制膜电位从−180到−60 mV时，HEK细胞中膜发生准线性位移；2)参考文献中的图4c。5)显示了当膜电位从0到120 mV相对于静止电位变化时，PC-12细胞施加在压电纳米带上的力的准线性依赖关系；3)参考文献中的图2A。6描述了当膜电位从−120变化到+60 mV时，HEK细胞中的准线性膜位移；4)参考文献中的图1H。7显示在HEK细胞中，随着刺激电压幅度从0到100 mV，光学相位变化的幅度呈准线性增加；5)参考文献中的图3E。8显示当膜电位通过膜片钳从−100变化到+100 mV时，在HEK细胞的边缘和中心区域测量到准线性的膜位移；以及6)我们也没有看到任何证据表明在动作电位范围内有拐点：从−70到+30 mV。在裁判中4偏离了这些实验观察，使得解释这些主张变得困难，特别是在最相关的图8a中，其中包括其对张等人的S模型(2)(由虚线黑线所示)的曲线图中的不一致。在这里，用相同的方程计算的膜张力变化比我们自己计算的(每0.1V∼10μN/m)大一个数量级，而我们的结果与文献[1]中的实验测量结果相吻合。2.我们找不到参考资料的补充材料。4在此基础上展开，但在任何情况下，总体结果都是相同的：实验数据仅支持与动作电位相关的电压范围内的准线性电压-张力关系。此外，正如我们在论文的介绍和讨论中提到的，已经提出了许多不同的模型来解释电动的机制，我们鼓励任何从事这一领域的理论建模的人使用所有可用的实验数据，包括我们的。
In PNAS (1), we report the full-field interferometric imaging of the dynamics of neuronal deformations during the action potential. The imaging methodology we describe provides a noninvasive approach to observation of the neural signaling and also allows scientists to verify their models with more degrees of freedom provided by the spatial distribution of the deformations, compared to previous single-point measurements. We also show that the mechanical model based on voltage-dependent membrane tension proposed by Zhang et al.(2) fits our observations. Farrell (3) argues that the membrane tension should change in a parabolic manner with the transmembrane voltage, with its maximum value at 16 mV, as proposed in their model (4). However, all of the experimental measurements of the voltage-dependent cellular deformations we are aware of demonstrate a quasi-linear relationship between the membrane tension and the transmembrane voltage: 1) figure 1c in ref. 2 demonstrates quasi-linear membrane displacement in HEK cells when the membrane potential was controlled from− 180 to− 60 mV by a patch clamp; 2) figure 4c in ref. 5 shows quasi-linear dependence of the force exerted by PC-12 cells on a piezoelectric nanoribbon when the membrane potential varied from 0 to 120 mV with respect to the resting potential; 3) figure 2A in ref. 6 depicts quasi-linear membrane displacement in HEK cells when the membrane potential varied from− 120 to+ 60 mV; 4) figure 1H in ref. 7 demonstrates a quasi-linear increase in amplitude of the optical phase change against the stimulus voltage amplitude ranging from 0 to 100 mV in HEK cells; 5) figure 3e in ref. 8 shows a quasi-linear membrane displacement measured at the edge and in the center regions of the HEK cells when the membrane potential was varied by a patch clamp from− 100 to+ 100 mV; and 6) we also have not seen any evidence of an inflection point within the range of action potential: from− 70 to+ 30 mV.The models suggested by Farrell et al. in ref. 4 depart from these experimental observations, making interpretation of these claims difficult, particularly in the most relevant figure 8a, which includes inconsistencies in its plot of Zhang et al.’s model (2)(shown by the dashed black line). Here, the calculation of the membrane tension change is one order of magnitude larger than our own calculation (∼ 10 μN/m per 0.1 V) using the same equation, while our result agrees with the experimental measurement in ref. 2. We were unable to find the supplementary material for ref. 4 that expands on that derivation, but in any case the overall outcome is the same: Experimental data support only a quasi-linear voltage–tension dependence in the voltage range relevant to the action potential. Furthermore, as we mention in the Introduction and Discussion of our paper, many different models have been proposed to explain the mechanism of electromotility, and we encourage anyone working on theoretical modeling in this field to use all of the available experimental data, including ours.