Institute of Health Care Engineering with European Testing Center for Medical Devices, Graz University of Technology, Graz, Austria.
Research Unit on Ion Channels and Cancer Biology, Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Medical University of Graz, Graz, Austria.
PLoS Comput Biol. 2021 Jun 22;17(6):e1009091. doi: 10.1371/journal.pcbi.1009091. eCollection 2021 Jun.
Lung cancer is still a leading cause of death worldwide. In recent years, knowledge has been obtained of the mechanisms modulating ion channel kinetics and thus of cell bioelectric properties, which is promising for oncological biomarkers and targets. The complex interplay of channel expression and its consequences on malignant processes, however, is still insufficiently understood. We here introduce the first approach of an in-silico whole-cell ion current model of a cancer cell, in particular of the A549 human lung adenocarcinoma, including the main functionally expressed ion channels in the plasma membrane as so far known. This hidden Markov-based model represents the electrophysiology behind proliferation of the A549 cell, describing its rhythmic oscillation of the membrane potential able to trigger the transition between cell cycle phases, and it predicts membrane potential changes over the cell cycle provoked by targeted ion channel modulation. This first A549 in-silico cell model opens up a deeper insight and understanding of possible ion channel interactions in tumor development and progression, and is a valuable tool for simulating altered ion channel function in lung cancer electrophysiology.
肺癌仍然是全球主要的死亡原因。近年来，人们对调节离子通道动力学的机制有了一定的了解，从而对肿瘤标志物和靶点有了新的认识。然而，通道表达的复杂相互作用及其对恶性过程的影响仍未得到充分理解。在这里，我们首次引入了一种基于计算机的全细胞膜电流模型，该模型特别针对人肺腺癌细胞系 A549，包括迄今为止已知的主要功能性表达的质膜离子通道。该基于隐马尔可夫模型的模型代表了 A549 细胞增殖背后的电生理学特性，描述了其膜电位的节律性振荡，这种振荡能够触发细胞周期各阶段之间的转变，并预测了靶向离子通道调节引起的细胞周期内的膜电位变化。这种用于 A549 细胞的第一个计算机模型能够更深入地了解肿瘤发生和发展过程中可能存在的离子通道相互作用，并且是模拟肺癌电生理学中改变离子通道功能的有价值的工具。
