时间延迟对细胞周期动力学的影响  

Influence of time delay on dynamics of cell cycle

作　　者：赵新军 李九智[3] 蒋中英 Zhao Xin-Jun;Li Jiu-Zhi;Jiang Zhong-Ying(Xinjiang Laboratory of Phase Transitions and Microstructures of Condensed Matter Physics,Yi Li Normal University,Yining 835000,China;Laboratory of Micro-Nano Electro Biosensors and Bionic Devices,Yi Li Normal University,Yining 835000,China;Department of Urology,Xinjiang Uygur Autonomous Region People’s Hospital,Urumqi 830000,China)

机构地区：[1]伊犁师范大学,新疆凝聚态相变与微结构实验室,伊宁835000 [2]伊犁师范大学,微纳电传感器技术与仿生器械实验室,伊宁835000 [3]新疆维吾尔自治区人民医院泌尿外科,乌鲁木齐830000

出　　处：《物理学报》2021年第20期383-391,共9页Acta Physica Sinica

基　　金：国家自然科学基金(批准号:21764015);伊犁师范大学博士科研启动基金(批准号:2020YSBS008);新疆自然科学基金联合基金(批准号:2019D01C333)资助的课题。

摘　　要：基于Hill动力学与Michaelis-Menten方程,建立理论模型研究CDK1(细胞周期蛋白依赖性蛋白激酶)/APC(后期促进复合物)系统振荡过程中,时间延迟对系统振荡动力学的影响.理论模型考虑CDK1-Plk1(Polo样蛋白质激酶)-APC通路中的时间延迟效应,研究发现,在不同时间延迟条件下,CDK1,Plk1和APC随时间演化呈现了周期性振荡特性,表明了细胞周期进程.随着时间延迟的增加,CDK1,Plk1和APC随时间演化的振荡周期变长、振幅增大,表明了时间延迟会改变体系的动力学特性.通过考察在高斯白噪声环境中的时间延迟效应,研究发现,噪声扰动明显地改变了CDK1随时间演化的动力学特性.在较小噪声环境中,CDK1/APC系统通过自调节时间延迟,改变振幅或振荡周期,重新自调控,使系统恢复稳定的周期性振荡.在较大噪声环境中,CDK1呈现了阻尼振荡模式.由此表明了较强的噪声,会使得CDK1/APC系统周期性振荡动力学出现较大改变,由于时间延迟,CDK1/APC振荡系统表现为从原有的周期性振荡转变为阻尼振荡,系统原有的振荡模式很难再恢复.理论结果进一步揭示了诸如非洲爪蟾胚胎等细胞周期过程中的时间延迟效应,可为设计调控细胞周期、阻断肿瘤转变的通路治疗方案提供理论依据.In this work,based on the Hill dynamics and Michaelis-Menten equation,a theoretical model is built to study the influence of time delay on the oscillation dynamics of a cyclin-dependent kinase 1(CDK1)/anaphasepromoting complex(APC)system.The theoretical model considers the time delay in the CDK1-polo-like protein kinase(P1 K1)-APC pathway.We find that under different time delay conditions,the CDK1,Plk1 and APC exhibit periodic oscillation characteristics over time,indicating cell cycle progression.With the increase of time delay,the oscillation periods and amplitudes of CDK1,Plk1 and APC increase,which indicates that the time delay will change the dynamic characteristics of the system.It implies that during the cell cycle,the status of the CDK1/APC oscillation system will show a long-term correlation with the biochemical reaction time of each component,such as CDK1,Plk1 and APC.This correlation is influenced by its past,and there is a timedelay effect.The additional correction will be made due to time delay.By investigating the time-delay effect in Gaussian white noise environment,we find that in the Gaussian white noise environment,the noise disturbance obviously changes the dynamic characteristics of CDK1 evolution with time.In a low-noise environment,the CDK1/APC system changes the oscillation amplitude or period through self-adjusting time delay,so that the system can restore the stable periodic oscillation,while in a high noise environment,CDK1 exhibits a damped oscillation,indicating that the periodic oscillation dynamics of the CDK1/APC system will be significantly changed by strong noise.In the CDK1/APC system oscillation process,the system adjusts the physiological response through a feedback mechanism.There is a time delay between the perception of the noise effect and the establishment of an appropriate physiological response.By different time delays,the system can adjust complex non-periodic chaotic rhythms with different time delays,and recover to produce a stable periodic physiological process.Owing

关 键 词：时间延迟 细胞周期 振荡动力学 

分 类 号：Q253[生物学—细胞生物学]