Modelling how lamellipodia-driven cells maintain persistent migration and interact with external barriers

Shubhadeep Sadhukhan, Cristina Martinez-Torres, Samo Penič, Carsten Beta, Aleš Iglič, Nir S Gov
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Abstract

Cell motility is fundamental to many biological processes, and cells exhibit a variety of migration patterns. Many motile cell types follow a universal law that connects their speed and persistency, a property that can originate from the intracellular transport of polarity cues due to the global actin retrograde flow. This mechanism was termed the ``Universal Coupling between cell Speed and Persistency"(UCSP). Here we implemented a simplified version of the UCSP mechanism in a coarse-grained ``minimal-cell" model, which is composed of a three-dimensional vesicle that contains curved active proteins. This model spontaneously forms a lamellipodia-like motile cell shape, which is however sensitive and can depolarize into a non-motile form due to random fluctuations or when interacting with external obstacles. The UCSP implementation introduces long-range inhibition, which stabilizes the motile phenotype. This allows our model to describe the robust polarity observed in cells and explain a large variety of cellular dynamics, such as the relation between cell speed and aspect ratio, cell-barrier scattering, and cellular oscillations in different types of geometric confinements.
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模拟叶状薄片驱动的细胞如何保持持续迁移并与外部障碍相互作用
细胞运动是许多生物过程的基础,细胞表现出多种迁移模式。许多运动细胞类型都遵循一种普遍规律,即它们的速度和持久性之间存在联系,这种特性可能源于全球肌动蛋白逆向流动引起的极性线索的胞内运输。这种机制被称为 "细胞速度与持久性之间的普遍耦合"(UCSP)。在这里,我们在一个粗粒度的 "最小细胞 "模型中实现了UCSP机制的简化版本,该模型由包含弯曲活性蛋白的三维囊泡组成。该模型会自发形成类似于叶状枝的运动细胞形状,但这种形状是敏感的,会因随机波动或与外部障碍物相互作用而去极化为非运动形式。UCSP 实现引入了长程抑制,从而稳定了运动表型。这使得我们的模型能够描述在细胞中观察到的稳健极性,并解释大量细胞动力学现象,如细胞速度与长宽比之间的关系、细胞-屏障散射以及不同类型几何约束中的细胞振荡。
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