Craig Erin M, Oprea Francesca, Alam Sajid, Grodsky Ania, Miller Kyle E
Central Washington University, Department of Physics, 400 E. University Way, Ellensburg, WA 98926-7422, USA.
Department of Integrative Biology, Michigan State University, East Lansing, MI 48824, USA.
bioRxiv. 2024 May 23:2024.05.22.595337. doi: 10.1101/2024.05.22.595337.
Axonal outgrowth, cell crawling, and cytokinesis utilize actomyosin, microtubule-based motors, cytoskeletal dynamics, and substrate adhesions to produce traction forces and bulk cellular motion. While it has long been appreciated that growth cones resemble crawling cells and that the mechanisms that drive cytokinesis help power cell crawling, they are typically viewed as unique processes. To better understand the relationship between these modes of motility, here, we developed a unified active fluid model of cytokinesis, amoeboid migration, mesenchymal migration, neuronal migration, and axonal outgrowth in terms of cytoskeletal flow, adhesions, viscosity, and force generation. Using numerical modeling, we fit subcellular velocity profiles of the motions of cytoskeletal structures and docked organelles from previously published studies to infer underlying patterns of force generation and adhesion. Our results indicate that, during cytokinesis, there is a primary converge zone at the cleavage furrow that drives flow towards it; adhesions are symmetric across the cell, and as a result, cells are stationary. In mesenchymal, amoeboid, and neuronal migration, the site of the converge zone shifts, and differences in adhesion between the front and back of the cell drive crawling. During neuronal migration and axonal outgrowth, the primary convergence zone lies within the growth cone, which drives actin retrograde flow in the P-domain and bulk anterograde flow of the axonal shaft. They differ in that during neuronal migration, the cell body is weakly attached to the substrate and thus moves forward at the same velocity as the axon. In contrast, during axonal outgrowth, the cell body strongly adheres to the substrate and remains stationary, resulting in a decrease in flow velocity away from the growth cone. The simplicity with which cytokinesis, cell crawling, and axonal outgrowth can be modeled by varying coefficients in a simple model suggests a deep connection between them.
轴突生长、细胞爬行和胞质分裂利用肌动球蛋白、基于微管的马达蛋白、细胞骨架动力学和底物黏附来产生牵引力和整体细胞运动。长期以来，人们一直认识到生长锥类似于爬行细胞，并且驱动胞质分裂的机制有助于推动细胞爬行，但它们通常被视为独特的过程。为了更好地理解这些运动模式之间的关系，在这里，我们根据细胞骨架流动、黏附、黏度和力的产生，开发了一个关于胞质分裂、阿米巴样迁移、间充质迁移、神经元迁移和轴突生长的统一活性流体模型。通过数值建模，我们拟合了先前发表研究中细胞骨架结构和对接细胞器运动的亚细胞速度分布，以推断潜在的力产生和黏附模式。我们的结果表明，在胞质分裂期间，在分裂沟处有一个主要的汇聚区，它驱动流向其流动；黏附在细胞两侧是对称的，因此细胞是静止的。在间充质、阿米巴样和神经元迁移中，汇聚区的位置发生变化，细胞前后黏附的差异驱动细胞爬行。在神经元迁移和轴突生长期间，主要汇聚区位于生长锥内，它驱动肌动蛋白在P结构域的逆行流动和轴突轴的整体顺行流动。它们的不同之处在于，在神经元迁移期间，细胞体与底物的附着较弱，因此以与轴突相同的速度向前移动。相比之下，在轴突生长期间，细胞体强烈黏附于底物并保持静止，导致远离生长锥的流速降低。通过在一个简单模型中改变系数就可以对胞质分裂、细胞爬行和轴突生长进行建模，这种简单性表明它们之间存在着深刻的联系。
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