论文标题
三部分轮廓动力学模型,以模拟和分析变形虫细胞运动性
Three-component contour dynamics model to simulate and analyze amoeboid cell motility
论文作者
论文摘要
变形虫细胞运动与多种生物医学应用有关,例如伤口愈合,癌症转移和胚胎形态发生。它的特征是与细胞膜的膨胀和缩回相关的细胞形状的明显变化,这导致了一种爬行的运动。尽管有现有的反向运动的计算模型,单个细胞的扩展和缩回成分的推断,相应的细胞分类以及参数制度的先验规范以实现特定的运动行为仍然是具有挑战性的开放问题。我们提出了一个新型模型的新型模型,该模型包括包含三个生物生物学动机成分的二维细胞轮廓:通过正规化膜缩回的膜缩回术语和两个确定性术语,该术语通过正规化轮廓轮廓的形状和面积来说明膜缩回术语。从数学上讲,这些对应于自兴奋的泊松点过程的强度,防护面积曲线变形流以及面积调节流。该模型用于生成各种定性不同的轮廓数据,例如极化和非极化的细胞轨道,这些轨道几乎与实验数据无法区分。在应用于实验细胞轨道的应用中,我们推断了突出成分,并检查了其与常用生物标志物的相关性:肌动蛋白浓度接近膜及其局部运动。由于模型的复杂性较低,参数估计是快速,直接的,并提供了一种基于两种运动类型的轮廓动力学分类的简单方法:变形虫和所谓的扇形类型。对于两种类型,我们使用模型有机体D. Discoideum的荧光成像数据分割的细胞轨道。在开源软件包Amoeepy中提供了该模型的实现。
Amoeboid cell motility is relevant in a wide variety of biomedical applications such as wound healing, cancer metastasis, and embryonic morphogenesis. It is characterized by pronounced changes of the cell shape associated with expansions and retractions of the cell membrane, which result in a crawling kind of locomotion. Despite existing computational models of amoeboid motion, the inference of expansion and retraction components of individual cells, the corresponding classification of cells, and the a priori specification of the parameter regime to achieve a specific motility behavior remain challenging open problems. We propose a novel model of the spatio-temporal evolution of two-dimensional cell contours comprising three biophysiologically motivated components: a stochastic term accounting for membrane protrusions and two deterministic terms accounting for membrane retractions by regularizing the shape and area of the contour. Mathematically, these correspond to the intensity of a self-exciting Poisson point process, the area-preserving curve-shortening flow, and an area adjustment flow. The model is used to generate contour data for a variety of qualitatively different, e.g., polarized and non-polarized, cell tracks that are hardly distinguishable from experimental data. In application to experimental cell tracks, we inferred the protrusion component and examined its correlation to commonly used biomarkers: the actin concentration close to the membrane and its local motion. Due to the low model complexity, parameter estimation is fast, straightforward and offers a simple way to classify contour dynamics based on two locomotion types: the amoeboid and a so-called fan-shaped type. For both types, we use cell tracks segmented from fluorescence imaging data of the model organism D. discoideum. An implementation of the model is provided within the open-source software package AmoePy.