scholarly journals A Cellular Potts Model for Analyzing Cell Migration across Constraining Pillar Arrays

Axioms ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 32
Author(s):  
Marco Scianna ◽  
Luigi Preziosi

Cell migration in highly constrained environments is fundamental in a wide variety of physiological and pathological phenomena. In particular, it has been experimentally shown that the migratory capacity of most cell lines depends on their ability to transmigrate through narrow constrictions, which in turn relies on their deformation capacity. In this respect, the nucleus, which occupies a large fraction of the cell volume and is substantially stiffer than the surrounding cytoplasm, imposes a major obstacle. This aspect has also been investigated with the use of microfluidic devices formed by dozens of arrays of aligned polymeric pillars that limit the available space for cell movement. Such experimental systems, in particular, in the designs developed by the groups of Denais and of Davidson, were here reproduced with a tailored version of the Cellular Potts model, a grid-based stochastic approach where cell dynamics are established by a Metropolis algorithm for energy minimization. The proposed model allowed quantitatively analyzing selected cell migratory determinants (e.g., the cell and nuclear speed and deformation, and forces acting at the nuclear membrane) in the case of different experimental setups. Most of the numerical results show a remarkable agreement with the corresponding empirical data.

2018 ◽  
Author(s):  
Inge M. N. Wortel ◽  
Ioana Niculescu ◽  
P. Martijn Kolijn ◽  
Nir Gov ◽  
Rob J. de Boer ◽  
...  

ABSTRACTCell migration is astoundingly diverse. Molecular signatures, cell-cell and cell-matrix interactions, and environmental structures each play their part in shaping cell motion, yielding numerous different cell morphologies and migration modes. Nevertheless, in recent years, a simple unifying law was found to describe cell migration across many different cell types and contexts: faster cells turn less frequently. Given this universal coupling between speed and persistence (UCSP), from a modelling perspective it is important to know whether computational models of cell migration capture this speed-persistence link. Here, we present an in-depth characterisation of an existing Cellular Potts Model (CPM). We first show that this model robustly reproduces the UCSP without having been designed for this task. Instead, we show that this fundamental law of migration emerges spontaneously through a crosstalk of intracellular mechanisms, cell shape, and environmental constraints, resembling the dynamic nature of cell migration in vivo. Our model also reveals how cell shape dynamics can further constrain cell motility by limiting both the speed and persistence a cell can reach, and how a rigid environment such as the skin can restrict cell motility even further. Our results further validate the CPM as a model of cell migration, and shed new light on the speed-persistence coupling that has emerged as a fundamental property of migrating cells.SIGNIFICANCEThe universal coupling between speed and persistence (UCSP) is the first general quantitative law describing motility patterns across the versatile spectrum of migrating cells. Here, we show – for the first time – that this migration law emerges spontaneously in an existing, highly popular computational model of cell migration. Studying the UCSP in entirely different model frameworks, not explicitly built with this law in mind, can help uncover how intracellular dynamics, cell shape, and environment interact to produce the diverse motility patterns observed in migrating cells.


2020 ◽  
Author(s):  
Pauli Tikka ◽  
Moritz Mercker ◽  
Ilya Skovorodkin ◽  
Ulla Saarela ◽  
Seppo Vainio ◽  
...  

Abstract During early kidney organogenesis, nephron progenitor (NP) cells move from the tip to the corner region of the ureteric bud (UB) branches in order to form the pretubular aggregate, the early structure giving rise to nephron formation. Chemotaxis and cell-cell adhesion differences are believed to drive cell patterning during this critical period of organogenesis, but the spatiotemporal organization of this process is incompletely understood. We applied a Cellular Potts model to explore to how these processes contribute to directed cell movement and aggregation. Model parameters were estimated based on fitting to experimental data obtained in ex vivo kidney explant and dissociation-reaggregation organoid culture studies. Our simulations indicated that optimal enrichment and aggregation of NP cells in the UB corner niche requires chemoattractant secretion from both the UB epithelial cells and the NP cells themselves, as well as differences in cell-cell adhesion energies. Furthermore, NP cells were observed, both experimentally and by modelling, to move at higher speed in the UB corner as compared to the tip region where they originated. The existence of different cell speed domains along the UB was confirmed using self-organizing map analysis. In summary, we demonstrated the suitability of a Cellular Potts Model approach to simulate cell movement and patterning during early nephrogenesis. Further refinement of the model should allow us to recapitulate the effects of developmental changes of cell phenotypes and molecular crosstalk during organ development.


Author(s):  
Inge M.N. Wortel ◽  
Ioana Niculescu ◽  
P. Martijn Kolijn ◽  
Nir Gov ◽  
Rob J. de Boer ◽  
...  

2016 ◽  
Vol 275 ◽  
pp. 57-70 ◽  
Author(s):  
R. Allena ◽  
M. Scianna ◽  
L. Preziosi

2020 ◽  
Author(s):  
Pauli Tikka ◽  
Moritz Mercker ◽  
Ilya Skovorodkin ◽  
Ulla Saarela ◽  
Seppo Vainio ◽  
...  

AbstractDuring early kidney organogenesis, nephron progenitor (NP) cells move from the tip to the corner region of the ureteric bud (UB) branches in order to form the pretubular aggregate, the early structure giving rise to nephron formation. Chemotaxis and cell-cell adhesion differences are believed to drive cell patterning during this critical period of organogenesis, but the spatiotemporal organization of this process is incompletely understood.We applied a Cellular Potts model to explore to how these processes contribute to directed cell movement and aggregation. Model parameters were estimated based on fitting to experimental data obtained in ex vivo kidney explant and dissociation-reaggregation organoid culture studies.Our simulations indicated that optimal enrichment and aggregation of NP cells in the UB corner niche requires chemoattractant secretion from both the UB epithelial cells and the NP cells themselves, as well as differences in cell-cell adhesion energies. Furthermore, NP cells were observed, both experimentally and by modelling, to move at higher speed in the UB corner as compared to the tip region where they originated. The existence of different cell speed domains along the UB was confirmed using self-organizing map analysis.In summary, we demonstrated the suitability of a Cellular Potts Model approach to simulate cell movement and patterning during early nephrogenesis. Further refinement of the model should allow us to recapitulate the effects of developmental changes of cell phenotypes and molecular crosstalk during organ development.Author SummaryThe emergence of tissue patterns during vertebrate development is a major interest of both experimental research and biocomputational modelling. In this study, we established a Cellular Potts Model to explore cellular processes during early kidney development. The goal was to elucidate movements and aggregations of nephron progenitor cells. These precursor cells derive from mesenchymal cells around the ureteric buds and eventually form the epithelial structure of the nephron. Moreover, we wanted to explore computationally the mechanisms how these cells segregate from metanephric mesenchyme and move towards the location where the nephron will be formed. Utilizing the Compucell3D simulation software, we developed a model which assumes that nephron progenitor movement and aggregation is governed by only two mechanisms, i.e. cell-cell adhesion differences between cell types and nephron progenitor cell chemotaxis in response to chemoattractant secretion from two sources. These sources were either the epithelial cells of a static ureteric bud and/or the nephron progenitor cells themselves. The simulations indicated faster average cell speeds near the ureteric bud corner, the target region of cell movement and aggregation, and slower speeds near the place of origin, the tip of ureteric bud. The results were validated by comparison of the model predictions with experimental data from two ex vivo embryonic kidney models and a computational optimization protocol.


2004 ◽  
Vol 15 (3) ◽  
pp. 982-989 ◽  
Author(s):  
Chun-Min Lo ◽  
Denis B. Buxton ◽  
Gregory C.H. Chua ◽  
Micah Dembo ◽  
Robert S. Adelstein ◽  
...  

Although myosin II is known to play an important role in cell migration, little is known about its specific functions. We have addressed the function of one of the isoforms of myosin II, myosin IIB, by analyzing the movement and mechanical characteristics of fibroblasts where this protein has been ablated by gene disruption. Myosin IIB null cells displayed multiple unstable and disorganized protrusions, although they were still able to generate a large fraction of traction forces when cultured on flexible polyacrylamide substrates. However, the traction forces were highly disorganized relative to the direction of cell migration. Analysis of cell migration patterns indicated an increase in speed and decrease in persistence, which were likely responsible for the defects in directional movements as demonstrated with Boyden chambers. In addition, unlike control cells, mutant cells failed to respond to mechanical signals such as compressing forces and changes in substrate rigidity. Immunofluorescence staining indicated that myosin IIB was localized preferentially along stress fibers in the interior region of the cell. Our results suggest that myosin IIB is involved not in propelling but in directing the cell movement, by coordinating protrusive activities and stabilizing the cell polarity.


RSC Advances ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 1875-1882
Author(s):  
Ronghe Xu ◽  
Xiaoli Zhao ◽  
Liqin Wang ◽  
Chuanwei Zhang ◽  
Yuze Mao ◽  
...  

An optimization approach based on the synthesis minimum energy was proposed for determining droplet wetting modes.


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