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

Shubhadeep Sadhukhan, Cristina Martinez-Torres, Samo Penic, Carsten Beta, Ales Iglic, 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.
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。许多运动细胞类型遵循一种普遍规律,将其速度和持久性联系起来,这种特性可能源于全球肌动蛋白逆流导致的细胞内极性线索运输。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,该模型由一个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,但它也很敏感,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,并解释各种细胞动力学,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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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