Das Jayajit
Battelle Center for Mathematical Medicine, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio; Biophysics Program and Departments of Pediatrics and Physics, The Ohio State University, Columbus, Ohio.
Biophys J. 2016 Mar 8;110(5):1180-90. doi: 10.1016/j.bpj.2016.01.022.
Single cells often generate precise responses by involving dissipative out-of-thermodynamic-equilibrium processes in signaling networks. The available free energy to fuel these processes could become limited depending on the metabolic state of an individual cell. How does limiting dissipation affect the kinetics of high-precision responses in single cells? I address this question in the context of a kinetic proofreading scheme used in a simple model of early-time T cell signaling. Using exact analytical calculations and numerical simulations, I show that limiting dissipation qualitatively changes the kinetics in single cells marked by emergence of slow kinetics, large cell-to-cell variations of copy numbers, temporally correlated stochastic events (dynamic facilitation), and ergodicity breaking. Thus, constraints in energy dissipation, in addition to negatively affecting ligand discrimination in T cells, can create a fundamental difficulty in determining single-cell kinetics from cell-population results.
单细胞通常通过在信号网络中涉及耗散性的非热力学平衡过程来产生精确的反应。为这些过程提供能量的可用自由能可能会因单个细胞的代谢状态而受到限制。限制耗散如何影响单细胞中高精度反应的动力学？我在早期T细胞信号传导的一个简单模型中使用的动力学校对方案的背景下解决这个问题。通过精确的解析计算和数值模拟，我表明限制耗散会定性地改变单细胞中的动力学，其特征是出现缓慢的动力学、拷贝数的细胞间大差异、时间相关的随机事件（动态促进）和遍历性破坏。因此，能量耗散的限制除了对T细胞中的配体识别产生负面影响外，还会在从细胞群体结果确定单细胞动力学方面造成根本性困难。
