Model of polarization and bistability of cell fragments
Model of polarization and bistability of cell fragments
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DOI：
10.1529/biophysj.107.110411
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发表时间：
2007-12-01
影响因子：
3.4
通讯作者：
Mogilner, Alex
中科院分区：
文献类型：
--
作者：
Kozlov, Michael M.;Mogilner, Alex
定向细胞运动先于细胞极化——细胞骨架和细胞形状前后不对称的发展。广泛的研究表明，在建立细胞极性时，多个信号通路之间存在复杂的时空反馈，但这种现象的物理机制仍然难以捉摸。基于对鱼角膜细胞的片状足碎片的观察，我们提出了细胞极化和双稳定性的纯热力学（不涉及信号传导）定量模型。该模型基于肌动蛋白聚合对细胞边缘施加的推力、细胞内肌球蛋白 II 提供的收缩力以及细胞膜的弹性张力之间的相互作用。我们计算了这些细胞内力产生的热力学功，并表明在短时间内，细胞力学可以用有效的能量函数来表征。具有两个最小值，描述由能垒分隔的两种稳定状态，并对应于非极化和极化细胞。该能量亲暗示的细胞动力学。 le 是双稳态的——细胞要么是圆盘形且静止的，要么是新月形且活动的——在有限的外部刺激下，它们之间可能发生转变，能够驱动系统越过宏观能垒。该模型解释了对角膜细胞碎片行为的观察，并生成有关细胞内力大小与细胞几何形状和运动性之间关系的定量预测。
Directed cell motility is preceded by cell polarization - development of a front- rear asymmetry of the cytoskeleton and the cell shape. Extensive studies implicated complex spatial- temporal feedbacks between multiple signaling pathways in establishing cell polarity, yet physical mechanisms of this phenomenon remain elusive. Based on observations of lamellipodial fragments of fish keratocyte cells, we suggest a purely thermodynamic ( not involving signaling) quantitative model of the cell polarization and bistability. The model is based on the interplay between pushing force exerted by F- actin polymerization on the cell edges, contractile force powered by myosin II across the cell, and elastic tension in the cell membrane. We calculate the thermodynamic work produced by these intracellular forces, and show that on the short timescale, the cell mechanics can be characterized by an effective energy pro. le with two minima that describe two stable states separated by an energy barrier and corresponding to the nonpolarized and polarized cells. Cell dynamics implied by this energy pro. le is bistable - the cell is either disk- shaped and stationary, or crescent- shaped and motile - with a possible transition between them upon a finite external stimulus able to drive the system over the macroscopic energy barrier. The model accounts for the observations of the keratocyte fragments' behavior and generates quantitative predictions about relations between the intracellular forces' magnitudes and the cell geometry and motility.