细胞质浓度：细胞生物学的老问题、新参数

doi:10.12211/2096-8280.2024-086

合成生物学 ›› 2025, Vol. 6 ›› Issue (3): 497-515.DOI: 10.12211/2096-8280.2024-086

细胞质浓度：细胞生物学的老问题、新参数

李倩¹, FERRELL JR.James E.²^,³, 陈于平¹

^1.中国科学院深圳先进技术研究院，定量合成生物学全国重点实验室，深圳合成生物学创新研究院，广东深圳 518055
^2.斯坦福大学医学院化学与系统生物学系，美国加利福尼亚州斯坦福 94305
^3.斯坦福大学医学院生物化学系，美国加利福尼亚州斯坦福 94305

收稿日期:2024-12-02 修回日期:2025-03-04 出版日期:2025-06-30 发布日期:2025-06-27
通讯作者: 陈于平
作者简介:李倩（1998—），女，科研助理。研究方向为细胞质浓度稳态调控。E-mail：qian.li2@siat.ac.cn
陈于平（1990—），男，副研究员，博士生导师。研究方向为细胞质稳态调控。 E-mail：yp.chen3@siat.ac.cn
基金资助:
国家重点研发计划“合成生物学”重点专项(2024YFA0919600);深圳合成生物学研究所启动经费项目(HSE49901)

Cytoplasmic concentration: an old question and a new parameter in cell biology

LI Qian¹, FERRELL JR. James E.²^,³, CHEN Yuping¹

^1.State Key Laboratory of Quantitative Synthetic Biology，Shenzhen Institute of Synthetic Biology，Shenzhen Institutes of Advanced Technology，Chinese Academy of Sciences，Shenzhen 518055，Guangdong，China
^2.Department of Chemical and Systems Biology，School of Medicine，Stanford University，Stanford 94305，California，USA
^3.Department of Biochemistry，School of Medicine，Stanford University，Stanford 94305，California，USA

Received:2024-12-02 Revised:2025-03-04 Online:2025-06-30 Published:2025-06-27
Contact: CHEN Yuping

摘要/Abstract

摘要：

细胞质浓度是细胞生理的重要参数，影响几乎所有生化反应，参与调节细胞生物学过程。近年来，随着显微技术、微流控技术以及合成生物学的发展，研究细胞质浓度的工具不断涌现，促进了对细胞质浓度稳态的调控机理及细胞质生物学的探索，增强了对细胞质浓度参与细胞生理调控的理解。本文介绍了监测细胞质浓度的新方法、新数据，归纳了细胞质浓度稳态调控机制，总结了细胞质浓度在生理生化过程中发挥的作用，从理论和实验角度探讨了细胞质浓度异质性的功能和调控机制，介绍并扩充了细胞质浓度在反应速率、稳态调节中的理论研究。目前对于细胞质浓度的研究在稳态决定机制、与其他生理过程的相互作用及合成生物学中的应用方面还有诸多难题亟待突破。细胞质浓度的探究正逐渐形成一个活跃的研究领域，在多学科交叉、理解生命、人类健康、合成细胞等方面将有重大进展。

关键词: 细胞质浓度, 稳态调控, 蛋白质合成, 生物质, 反应速率, 负反馈调节, 扩散受限

Abstract:

Cytoplasmic concentration is an important parameter in cell physiology, influencing almost all biochemical reactions, playing key roles in regulating various cellular biological processes. However, studying cytoplasmic concentration has been particularly challenging due to its inherent complexity, the difficulty of direct manipulation, and the lack of precise measurement techniques for intact cells. In recent years, advances in microscopy, microfluidics, and synthetic biology have led to the development of novel tools for studying cytoplasmic concentration, such as Quantitative Phase Microscopy, Stimulated Raman Scattering Microscopy, and Genetically Encoded Multimers for single-particle tracking, etc. These advanced tools have enabled researchers to explore the regulation of cytoplasmic concentration, mechanism of the concentration homeostasis, and their influences on cellular physiology, providing deeper insights into their roles in physiological regulations. In this review, we explore both historical and recent advances in methods and overview data regarding cytoplasmic concentration, summarize the molecular and systematic mechanisms that govern its homeostatic regulation, and highlight its roles in physiological and biochemical processes. Specifically, we discuss the key biological processes that influence cytoplasmic concentration, including mitotic swelling, genome dilution, protein synthesis and degradation, and importantly, the heterogeneity of cytoplasmic concentration that arises from local subcellular structure and thermodynamic fluctuation. Furthermore, we expand on connections between cytoplasmic concentration, cellular aging, signal transduction, cellular differentiation, and microtubule assembly dynamics. Additionally, we explore the theoretical interpretation of cytoplasmic concentration in reaction kinetics and its homeostatic regulation, providing evidence from both experimental and theoretical studies on the prevalence of diffusion-limited reactions in biological systems. Despite these advances, significant challenges remain in fully understanding underlying mechanisms of cytoplasmic concentration homeostasis, its complex interactions with other physiological processes, and its potential applications in synthetic biology. Research on cytoplasmic concentration is rapidly evolving into an active field of study, promising major breakthroughs in understanding fundamentals of cellular life, improvement of human health, and engineering of synthetic cells.

Key words: cytoplasmic concentration, homeostatic control, protein synthesis, biomass, reaction rate, negative feedback regulation, diffusion limit

中图分类号:

Q816

李倩, FERRELL JR.James E., 陈于平. 细胞质浓度：细胞生物学的老问题、新参数[J]. 合成生物学, 2025, 6(3): 497-515.

LI Qian, FERRELL JR. James E., CHEN Yuping. Cytoplasmic concentration: an old question and a new parameter in cell biology[J]. Synthetic Biology Journal, 2025, 6(3): 497-515.

图/表 4

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细胞生理	细胞质浓度（变化前为100%）	浓度变化原因	后果	参考文献
有丝分裂肿胀	80%～90%	未知	未知	[46]
配子成熟	增加	排水	配子抗逆性增加	[75-76]
血细胞成熟	增加或减少；血红细胞细胞质浓度最大；单核细胞其次	血红细胞：血红蛋白大量合成	血红细胞携氧量增加	[34,47,77]
成骨细胞成熟	50%	细胞分化，体积增加	骨骼发育	[78]
渗透压	64%～155%	渗透压改变	微管聚合速率变化范围64%～477%；微管解聚速率变化范围42%～645%	[15]
翻译/降解	10%～200%	人工浓缩、稀释	翻译速度先增加后降低，降解速度增加	[13]
基因组稀释	cdc28-13突变体：66%	限制温度培养，细胞周期停滞，细胞体积增加	基因表达激活停滞；基因组稳定性降低	[79]
衰老	hTERT-RPE1细胞：降低（体积增至588%）；MCF7细胞：降低（体积增至262%）	Palbociclib处理，细胞体积增加	激活p53-p21信号传导；53BP1不再修复DNA损伤；有丝分裂失败；基因组不稳定性；细胞周期永久退出	[80]

细胞生理	细胞质浓度（变化前为100%）	浓度变化原因	后果	参考文献
有丝分裂肿胀	80%～90%	未知	未知	[46]
配子成熟	增加	排水	配子抗逆性增加	[75-76]
血细胞成熟	增加或减少；血红细胞细胞质浓度最大；单核细胞其次	血红细胞：血红蛋白大量合成	血红细胞携氧量增加	[34,47,77]
成骨细胞成熟	50%	细胞分化，体积增加	骨骼发育	[78]
渗透压	64%～155%	渗透压改变	微管聚合速率变化范围64%～477%；微管解聚速率变化范围42%～645%	[15]
翻译/降解	10%～200%	人工浓缩、稀释	翻译速度先增加后降低，降解速度增加	[13]
基因组稀释	cdc28-13突变体：66%	限制温度培养，细胞周期停滞，细胞体积增加	基因表达激活停滞；基因组稳定性降低	[79]
衰老	hTERT-RPE1细胞：降低（体积增至588%）；MCF7细胞：降低（体积增至262%）	Palbociclib处理，细胞体积增加	激活p53-p21信号传导；53BP1不再修复DNA损伤；有丝分裂失败；基因组不稳定性；细胞周期永久退出	[80]

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细胞质浓度：细胞生物学的老问题、新参数

Cytoplasmic concentration: an old question and a new parameter in cell biology

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