Integrating transient cellular and nuclear motions to comprehensively describe cell migration patterns (original) (raw)
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On the synchrony of morphological and molecular signaling events in cell migration
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics), 2009
This paper investigates the dynamics of cell migration, which is the movement of a cell towards a certain target area. More specifically, the objective is to analyze the causal interdependence between cellularmorphological events and molecular-signaling events. To this end, a novel data analysis method is developed: first the local morphological changes and molecular signaling events are determined by means of edge evolution tracking (EET), next the interdependence of those events is quantified through the method of stochastic event synchrony (SES). The proposed method is applied to time-lapse fluorescence resonance energy transfer (FRET) images of Rac1 activity in motile HT1080 cells; the protein Rac1 is well known to induce filamentous structures that enable cells to migrate. Results show a significant delay between local Rac1 activity events and morphological events. This observation provides new insights into the dynamic relationship between cellular-morphological change and molecular-signaling of migrating cells, and may pave the way to novel biophysical models of cell migration.
Taking Aim at Moving Targets in Computational Cell Migration
Trends in Cell Biology, 2015
Cell migration is central to the development and maintenance of multicellular organisms. Fundamental understanding of cell migration can, for example, direct novel therapeutic strategies to control invasive tumor cells. However, the study of cell migration yields an overabundance of experimental data that require demanding processing and analysis for results extraction. Computational methods and tools have therefore become essential in the quantification and modeling of cell migration data. We review computational approaches for the key tasks in the quantification of in vitro cell migration: image pre-processing, motion estimation and feature extraction. Moreover, we summarize the current state-of-the-art for in silico modeling of cell migration. Finally, we provide a list of available software tools for cell migration to assist researchers in choosing the most appropriate solution for their needs. Computational Cell Migration in a Nutshell Cell migration plays a fundamental role in physiological phenomena including neural development, wound healing, and immune function, as well as in disorders such as neurological diseases, fibrosis, and cancer metastasis [1-8]. Investigation of cell migration is therefore essential for successful intervention in physiological and pathological phenomena [9-12]. A major driver in the advance of cell migration research has been the evolution of instrumentation (microscopes and cameras) and the corresponding development of experimental tools and biological models. Indeed, 2D in vitro assays [13,14] have recently given way to more sophisticated two-and-a-half-dimensional (2.5D) and 3D approaches [15,16] which more faithfully represent the tissue environment. Because in vivo experiments are difficult and costly, in vitro and ex vivo setups are widely used, especially in drug compound and gene screening [17,18]. This review therefore primarily focuses on the quantification of cell migration in in vitro setups, while we refer the reader to specific literature on in vivo work [19-23].
Signaling pathways that control cell migration: models and analysis
Wiley interdisciplinary reviews. Systems biology and medicine
Dissecting the intracellular signaling mechanisms that govern the movement of eukaryotic cells presents a major challenge, not only because of the large number of molecular players involved, but even more so because of the dynamic nature of their regulation by both biochemical and mechanical interactions. Computational modeling and analysis have emerged as useful tools for understanding how the physical properties of cells and their microenvironment are coupled with certain biochemical pathways to actuate and control cell motility. In this focused review, we highlight some of the more recent applications of quantitative modeling and analysis in the field of cell migration. Both in modeling and experiment, it has been prudent to follow a reductionist approach in order to characterize what are arguably the principal modules: spatial polarization of signaling pathways, regulation of the actin cytoskeleton, and dynamics of focal adhesions. While it is important that we 'cut our teet...
Imaging the Molecular Machines That Power Cell Migration
Methods in Molecular Biology, 2018
Animal cell migration constitutes a complex process involving a multitude of forces generated and maintained by the actin cytoskeleton. Dynamic changes of the cell surface, for instance to effect cell edge protrusion, are at the core of initiating migratory processes, both in tissue culture models and whole animals. Here we sketch different aspects of imaging representative molecular constituents in such actin-driven processes, which power and regulate the polymerisation of actin filaments into bundles and networks, constituting the building blocks of such protrusions. The examples presented illustrate both the diversity of subcellular distributions of distinct molecular components, according to their function, and the complexity of dynamic changes in protrusion size, shape, and/or orientation in 3D. Considering these dynamics helps mechanistically connecting subcellular distributions of molecular machines driving protrusion and migration with their biochemical function.
qCMA: A Desktop Application for Quantitative Collective Cell Migration Analysis
Journal of biomolecular screening, 2012
Collective migration is an important cellular trait, which is intensely studied by both basic and translational researchers. Investigation of the underlying mechanisms necessitates high-throughput assays and computational algorithms capable of generating reproducible quantitative measurements of cell migration. We present a desktop tool that can be used easily by any researcher, to quantify both fluorescent and phase-contrast images produced in the course of commonly used gap closure ("scratch," "wound healing") collective migration assays. The software has a simple graphical interface that allows the user to tune the relevant parameters and process large numbers of images (or movies). The output contains segmented images and the numerical values inferred from them, allowing easy quantitative analysis of the results.
A novel approach to characterizing cell migration
2019
Cancer cell metastasis has been responsible for the vast majority of cancer-related deaths in the United States. The processes involved in cancer cell metastasis, such as extravasation and intravasation, are driven by cell motility. The conventional method of characterizing cell motility typically involved imaging live cells under a microscope for several hours and tracking cells’ trajectories manually with the help of computer software, and this method is highly inefficient and time-consuming for obtaining cell motility information. This dissertation aims to develop a new method to quantitatively characterize cell motility based on the spatial distribution of cells in clones at a specific time point. A simulation study was first performed to evaluate the correlation between cell spatial distribution in the clones and cell motility. Clonal distributions of cells were generated at the 72 hr time point from computer-simulated cell trajectories based on the PRW model for clone sizes of...
Plasticity in the Macromolecular-Scale Causal Networks of Cell Migration
PLoS ONE, 2014
Heterogeneous and dynamic single cell migration behaviours arise from a complex multi-scale signalling network comprising both molecular components and macromolecular modules, among which cell-matrix adhesions and F-actin directly mediate migration. To date, the global wiring architecture characterizing this network remains poorly defined. It is also unclear whether such a wiring pattern may be stable and generalizable to different conditions, or plastic and context dependent. Here, synchronous imaging-based quantification of migration system organization, represented by 87 morphological and dynamic macromolecular module features, and migration system behaviour, i.e., migration speed, facilitated Granger causality analysis. We thereby leveraged natural cellular heterogeneity to begin mapping the directionally specific causal wiring between organizational and behavioural features of the cell migration system. This represents an important advance on commonly used correlative analyses that do not resolve causal directionality. We identified organizational features such as adhesion stability and adhesion F-actin content that, as anticipated, causally influenced cell migration speed. Strikingly, we also found that cell speed can exert causal influence over organizational features, including cell shape and adhesion complex location, thus revealing causality in directions contradictory to previous expectations. Importantly, by comparing unperturbed and signalling-modulated cells, we provide proof-of-principle that causal interaction patterns are in fact plastic and context dependent, rather than stable and generalizable.
Nature Communications, 2017
Understanding the mechanisms of collective cell migration is crucial for cancer metastasis, wound healing and many developmental processes. Imaging a migrating cluster in vivo is feasible, but the quantification of individual cell behaviours remains challenging. We have developed an image analysis toolkit, CCMToolKit, to quantify the Drosophila border cell system. In addition to chaotic motion, previous studies reported that the migrating cells are able to migrate in a highly coordinated pattern. We quantify the rotating and running migration modes in 3D while also observing a range of intermediate behaviours. Running mode is driven by cluster external protrusions. Rotating mode is associated with cluster internal cell extensions that could not be easily characterized. Although the cluster moves slower while rotating, individual cells retain their mobility and are in fact slightly more active than in running mode. We also show that individual cells may exchange positions during migr...
Multiscale Cues Drive Collective Cell Migration
Scientific reports, 2016
To investigate complex biophysical relationships driving directed cell migration, we developed a biomimetic platform that allows perturbation of microscale geometric constraints with concomitant nanoscale contact guidance architectures. This permits us to elucidate the influence, and parse out the relative contribution, of multiscale features, and define how these physical inputs are jointly processed with oncogenic signaling. We demonstrate that collective cell migration is profoundly enhanced by the addition of contract guidance cues when not otherwise constrained. However, while nanoscale cues promoted migration in all cases, microscale directed migration cues are dominant as the geometric constraint narrows, a behavior that is well explained by stochastic diffusion anisotropy modeling. Further, oncogene activation (i.e. mutant PIK3CA) resulted in profoundly increased migration where extracellular multiscale directed migration cues and intrinsic signaling synergistically conspire...
The Interplay Between Cell-Cell and Cell-Matrix Forces Regulates Cell Migration Dynamics
Biophysical Journal, 2019
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