悬浮态上皮细胞粘附的力学–化学耦合模型及数值模拟
MECHANOCHEMICAL COUPLING MODEL AND NUMERICAL SIMULATION FOR CELL-CELL ADHESION IN SUSPENDED EPITHELIAL CELLS
查看参考文献37篇
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文摘
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上皮细胞通过局部募集上皮性钙粘附蛋白(E-cadherin)建立胞间粘着连接,实验证实该过程受到肌球蛋白皮层张力的调控.为了从系统层面阐明粘着连接形成动力学过程,本文考察皮层张力调控肌动蛋白(F-actin)解聚从而参与E-cadherin级联转导,同时以马达–离合器机制模拟两细胞相互作用,据此构建可反映悬浮态细胞粘附的力学–化学耦合数学模型;对整体包含随机点源的非线性反应–扩散方程组与平衡微分方程耦合系统采取了自行发展的格子Boltzmann–粒子法与蒙特–卡洛法数值求解.数值模拟表明,由收缩性肌球蛋白(myosin-II)拉动胞间E-cadherin成键可提升皮层张力,进而降低F-actin解聚速率﹑锚定更多的E-cadherin;所构成的力学反馈回路展现出时空效应,可帮助E-cadherin在接触区建立初始极性; E-cadherin形成顺式二聚体则将初始极性放大,导致接触区E-cadherin展现起始、快速增长及慢速增长的积聚动力学特征.皮层呈松散结构时刚度较小,可通过延长胞间E-cadherin成键寿命提升张力,而接触区弧度适中时(≈ 1.2 rad) E-cadherin峰值最高;两者可分别作为启动力学反馈回路及调控粘着连接成熟度的有效手段. |
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其他语种文摘
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Epithelial cells develop adherens junctions via local recruitment of a transmembrane receptor, named Ecadherin, whose activity is dependent on Ca 2+ signal. Growing evidences indicate the importance of tensile forces within actomyosin cortex, yet a system-level understanding for the mechanosensitive responses of cell-cell contacts remains unclear. Here, we constructed a mechanochemical coupling model, in which the tensile forces presented at adherens junctions participated in the interactions between myosin contractility, actin dynamics and local E-cadherin recruitment, which together, formed a mechanical feedback loop (MFL). The mechanical interactions between a pair of epithelial cells were treated by a motor-clutch mechanism. The in-house developed lattice-Boltzmann particle (LBP)-D1Q3 method, which had been embedded with a simple Monte-Carlo method, was adopted to solve the coupled nonlinear reactiondiffusion equations, which had stochastic reaction terms, and were coupled with the equilibrium differential equation. The numerical simulation results indicate that the spatiotemporal effects of MFL may arise an initial anisotropy in the distribution pattern of E-cadherin, which could be further amplified by “cis” interactions between E-cadherins from the same cell surface. The model thus confirms three distinct phases in the profile of E-cadherin accumulation at the center of contact zone, which are initial, rapid increase, and slowly increase, as observed experimentally. Furthermore, local recruitment of E-cadherin can be mechanically regulated by either the elastic modulus of actomyosin cortex or the extent of cell-cell contact, whereupon the highest E-cadherin density takes place at 1.2 rad. Accordingly, decreasing the elastic modulus of actomyosin cortex may thus act as a triggering mechanism for MFL while the length of cell-cell contact is denoted as a controller of the maturity of adherens junctions. |
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来源
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力学学报
,2020,52(3):854-863 【核心库】
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DOI
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10.6052/0459-1879-20-011
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关键词
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粘着连接
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数学模型
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格子玻尔兹曼
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地址
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宁波大学机械工程与力学学院, 浙江, 宁波, 315211
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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
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中国科学院大学工程科学学院, 北京, 100049
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语种
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中文 |
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文献类型
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研究性论文 |
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ISSN
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0459-1879 |
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学科
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生物物理学 |
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基金
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国家自然科学基金资助项目
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文献收藏号
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CSCD:6734914
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