论文标题
通过正则化轮廓流对变形虫细胞运动中突出动力学分析
Analysis of protrusion dynamics in amoeboid cell motility by means of regularized contour flows
论文作者
论文摘要
变形虫细胞运动对于包括伤口愈合,胚胎形态发生和癌症转移的广泛生物学过程至关重要。它依赖于细胞形状变化的复杂动力学模式,这些变化对数学建模构成了长期挑战,并提出了对自动化和可重现方法的需求,以从图像序列中提取定量形态特征。在这里,我们介绍了一种理论框架和一种计算方法,用于从分段显微镜图像的堆栈中获得时空轮廓动力学的平滑表示。基于高斯过程回归,我们提出了一个正规化轮廓流的单参数家族,该家族使我们能够在连续的单元格轮廓之间连续跟踪参考点(虚拟标记)。我们使用这种方法来定义移动电池边界上的坐标系,并在此参考框架中表示不同的局部几何量。特别是,我们引入了局部标记物分散剂,以识别局部膜扩展,并提供一种完全自动化的方法来提取此类扩展的特性,包括其面积和增长时间。该方法可作为一个名为Amoepy的开源软件包,这是一种基于Python的工具箱,用于分析变形虫细胞运动性(基于延时显微镜数据),包括图形用户界面和详细文档。由于我们的框架的数学严格性,我们设想它将用于开发新型细胞运动模型。我们主要使用社交变形虫迪斯特尔迪斯特尔的实验数据来说明和验证我们的方法。
Amoeboid cell motility is essential for a wide range of biological processes including wound healing, embryonic morphogenesis, and cancer metastasis. It relies on complex dynamical patterns of cell shape changes that pose long-standing challenges to mathematical modeling and raise a need for automated and reproducible approaches to extract quantitative morphological features from image sequences. Here, we introduce a theoretical framework and a computational method for obtaining smooth representations of the spatiotemporal contour dynamics from stacks of segmented microscopy images. Based on a Gaussian process regression we propose a one-parameter family of regularized contour flows that allows us to continuously track reference points (virtual markers) between successive cell contours. We use this approach to define a coordinate system on the moving cell boundary and to represent different local geometric quantities in this frame of reference. In particular, we introduce the local marker dispersion as a measure to identify localized membrane expansions and provide a fully automated way to extract the properties of such expansions, including their area and growth time. The methods are available as an open-source software package called AmoePy, a Python-based toolbox for analyzing amoeboid cell motility (based on time-lapse microscopy data), including a graphical user interface and detailed documentation. Due to the mathematical rigor of our framework, we envision it to be of use for the development of novel cell motility models. We mainly use experimental data of the social amoeba Dictyostelium discoideum to illustrate and validate our approach.