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CD44-配体相互作用的生物力学与功能调控
BIOMECHANICS AND FUNCTIONAL REGULATIONS OF CD44-LIGAND INTERACTIONS

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李林达 1   丁奇寒 2,3   陈深宝 2,3   吕守芹 2,3   龙勉 2,3   郭兴明 1  
文摘 作为一种广谱表达的细胞粘附分子, I型跨膜糖蛋白CD44(cluster of differentiation 44)参与细胞增殖、分化、迁移,血管生成等生物学过程,对于介导细胞信号转导,调节组织稳态等功能具有关键作用.特别地, CD44-选择素、CD44-透明质酸相互作用介导的细胞粘附动力学在经典炎症反应、肿瘤转移或组织特异的肝脏免疫中具有重要作用.该综述分别从细胞层次粘附动力学、二维与三维条件下的分子层次反应动力学、原子层次微观结构以及胞内信号转导通路等方面综述了CD44-选择素、CD44-透明质酸相互作用的研究进展及尚待回答的生物力学问题.力学、物理因素对生命活动的不可或缺性逐渐被研究者们接受,力学医学、力学免疫学、力学组学等新概念相继提出.生理、病理条件下, CD44-配体相互作用介导的细胞粘附必将受到血流剪切、基底硬度等力学、物理微环境的调控,但是其调控机制还远不清楚.基于此,本文就CD44-配体相互作用相关的未来研究方向做出展望,主要包括:力学、物理因素如何调控CD44-配体相互作用介导的细胞粘附动力学及其内在机制; CD44-配体相互作用反应动力学的力学调控规律及结构基础是什么;以及力学作用下CD44-配体相互作用原子层次的微观结构如何发生动态演化.本文可为深入理解CD44-配体相互作用的生物学功能及其结构功能关系提供线索.
其他语种文摘 As a widely expressed cellular adhesion molecule, type I transmembrane glycoprotein CD44 is crucial in cell proliferation, differentiation, migration, angiogenesis and other biological processes to induce intracellular signal transduction and regulate tissue homeostasis. Especially, cell adhesion dynamics mediated by CD44-selectin and CD44- hyaluronic acid (HA) interactions play key roles in classic inflammatory cascade, tumor metastasis, or tissue-specific liver immunity. This review discussed the progresses and remaining issues of CD44 selectin and CD44-HA interactions in various aspects of cellular adhesion dynamics, two- and three-dimensional molecular reaction kinetics, atomic microstructural features, and intracellular signal transduction pathways. Nowadays, the importance of mechanical and physical factors to biological activities has been gradually accepted by scientific community. New concepts such as mechanomedicine, mechanoimmunology and mechanomics have been put forward one after another. Under physiological or pathological conditions, cell adhesion mediated by CD44-ligand interactions are regulated by in vivo mechanical and physical cues such as blood shear or tissue stiffness, but their regulatory mechanisms are still unclear. From that on, future perspectives related to CD44-ligand interaction were also proposed in this review as follows: how mechanical and physical factors regulate cellular adhesion dynamics and intrinsic mechanism mediated by CD44-ligand interactions; what the mechanical regulation features of molecular reaction kinetics of CD44-ligand interactions and corresponding structural bases are; and how the atomic-level microstructures of CD44-ligand binding evolve dynamically under mechanical forces. This review provides clues for further understanding the biological functions and structure-function relationship of CD44-ligand interactions.
来源 力学学报 ,2021,53(2):539-553 【核心库】
DOI 10.6052/0459-1879-20-313
关键词 CD44 ; 选择素 ; 透明质酸 ; 细胞粘附 ; 力学调控 ; 炎症反应
地址

1. 重庆大学生物工程学院, 生物流变科学与技术教育部重点实验室, 重庆, 400044  

2. 中国科学院力学研究所生物力学与生物工程中心, 中国科学院微重力重点实验室;;工程化构建与力学生物学北京市重点实验室, 北京, 100190  

3. 中国科学院大学工程科学学院, 北京, 101408

语种 中文
文献类型 研究性论文
ISSN 0459-1879
学科 生物物理学
基金 国家自然科学基金资助项目
文献收藏号 CSCD:6917587

参考文献 共 127 共7页

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