模型化研究两细胞间基因、蛋白耦合振荡中的噪声效应  

Theoretical study on the effect of noise in the coupled oscillation of genes and proteins between two cells

作　　者：苏瑞 李九智[3] 李循[3] 王书恒 刘彼得 赵新军 SU Rui;LI Jiu-Zhi;LI Xun;WANG Shu-Heng;LIU Bi-De;ZHAO Xin-Jun(Xinjiang Laboratory of Phase Transitions and Microstructures in Condensed Maters,College of Physical Science and Technology,Yili Normal University,Yining 835000,China;Laboratory of Micro-Nano Electro Biosensors and Bionic Devices,Yili Normal University,Yining 835000,China;Department of Urology,the Xinjiang Uygur Autonomous Region People's Hospital,Urumqi 830000,China)

机构地区：[1]伊犁师范大学物理科学与技术学院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：《原子与分子物理学报》2024年第4期149-158,共10页Journal of Atomic and Molecular Physics

基　　金：国家自然科学基金(22163011);伊犁师范大学提升学科综合实力专项(22XKZY09)。

摘　　要：本文基于Hill动力学与Michaelis-Menten方程,建立理论模型研究两细胞间基因、蛋白耦合振荡中的噪声效应.研究发现,在Notch信号通路中,两细胞间基因、蛋白耦合振荡呈现了周期振荡特性,表明了细胞间信号传导的同步振荡特性.“内在”噪声和“外在”噪声对两细胞间基因、蛋白耦合振荡有着不同的作用.内噪声有利于细胞间Notch信号通路中各基因、蛋白表达再次提升.外噪声诱导通路中基因、蛋白的表达水平降低,周期振荡变得阻尼.内、外噪声共同作用不仅可使得基因表达适当并呈现出持续振荡模式,而且还可使得细胞间基因转录合成相应的蛋白过程呈现出持续振荡模式.从而表明了基因表达的内、外噪声共同作用有利于控制细胞间基因激活、蛋白合成保持周期节律性.本文理论结果揭示了内外噪声对细胞间Notch信号通路动力学的一种调控机制,确定了内外噪声各自的调控效应,澄清了内外噪声共同作用调控体系持续周期振荡的物理机制,理论结果符合实验,可为设计阻止Notch体系基因、蛋白变异导致的多种疾病和癌症的通路治疗方案提供理论依据.In this paper,based on Hill dynamics and Michaelis-Menten equation,a theoretical model is established to study the noise effect in the coupled oscillation of genes and proteins between two cells.We found that in the Notch signaling pathway,the coupled oscillations of genes and proteins between two cells exhibit periodic oscillation characteristics,indicating the synchronous oscillation characteristics of intercellular signaling."Intrinsic"noise and"external"noise have different effects on the coupled oscillation of genes and proteins between two cells.The internal noise is beneficial to increase the expression of genes and proteins in the intercellular Notch signaling pathway again.The expression levels of genes and proteins in external noise-induced pathways decrease,and periodic oscillations become damped.The combined action of internal and external noise can not only make gene expression appropriate and present a continuous oscillation pattern,but also make the corresponding protein process of gene transcription and synthesis between cells show a continuous oscillation mode.It shows that the internal and external noise of gene expression is beneficial to control the gene activation between cells and maintain the periodic rhythm of protein synthesis.The theoretical results in this paper reveal a regulatory mechanism of internal and external noise on the dynamics of the intercellular Notch signaling pathway.The respective regulatory effects of internal and external noise can be determined by our calculations,which clarify the physical mechanism of the continuous periodic oscillation of the regulation system under the combined effect of internal and external noise.The theoretical results are consistent with the experiments.It can provide a theoretical basis for the design of pathway therapies to prevent various diseases and cancers caused by Notch system gene and protein mutations.

关 键 词：细胞间基因、蛋白 耦合振荡 噪声 

分 类 号：Q492[生物学—生理学]