scholarly journals Computational modelling of cell chain migration reveals mechanisms that sustain follow-the-leader behaviour

2012 ◽  
Vol 9 (72) ◽  
pp. 1576-1588 ◽  
Author(s):  
Michelle L. Wynn ◽  
Paul M. Kulesa ◽  
Santiago Schnell
Keyword(s):  
Cancer Metastasis ◽  
Computational Modelling ◽  
Cell Movement ◽  
Cell Contact ◽  
Model Parameters ◽  
Directional Bias ◽  
Agent Based ◽  
Chain Migration ◽  
A Chain ◽  
Cell Cell

Follow-the-leader chain migration is a striking cell migratory behaviour observed during vertebrate development, adult neurogenesis and cancer metastasis. Although cell–cell contact and extracellular matrix (ECM) cues have been proposed to promote this phenomenon, mechanisms that underlie chain migration persistence remain unclear. Here, we developed a quantitative agent-based modelling framework to test mechanistic hypotheses of chain migration persistence. We defined chain migration and its persistence based on evidence from the highly migratory neural crest model system, where cells within a chain extend and retract filopodia in short-lived cell contacts and move together as a collective. In our agent-based simulations, we began with a set of agents arranged as a chain and systematically probed the influence of model parameters to identify factors critical to the maintenance of the chain migration pattern. We discovered that chain migration persistence requires a high degree of directional bias in both lead and follower cells towards the target. Chain migration persistence was also promoted when lead cells maintained cell contact with followers, but not vice-versa. Finally, providing a path of least resistance in the ECM was not sufficient alone to drive chain persistence. Our results indicate that chain migration persistence depends on the interplay of directional cell movement and biased cell–cell contact.

scholarly journals Computational Modelling of Nephron Progenitor Cell Movement and Aggregation During Kidney Organogenesis

2020 ◽  
Author(s):  
Pauli Tikka ◽  
Moritz Mercker ◽  
Ilya Skovorodkin ◽  
Ulla Saarela ◽  
Seppo Vainio ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Potts Model ◽  
Ex Vivo ◽  
Computational Modelling ◽  
Cell Movement ◽  
Model Parameters ◽  
Cellular Potts Model ◽  
Kidney Organogenesis ◽  
Nephron Progenitor ◽  
Cell Cell

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.

scholarly journals DEBUSSY 2.0: the new release of a Debye user system for nanocrystalline and/or disordered materials

2015 ◽  
Vol 48 (6) ◽  
pp. 2026-2032 ◽  
Author(s):  
Antonio Cervellino ◽  
Ruggero Frison ◽  
Federica Bertolotti ◽  
Antonietta Guagliardi
Keyword(s):  
Function Analysis ◽  
Computational Modelling ◽  
Site Occupancy ◽  
Group Symmetry ◽  
Model Parameters ◽  
General Strategy ◽  
Debye Function ◽  
Shape Information ◽  
Size Dependent ◽  
A Chain

The new release ofDEBUSSYis introduced, a free open-source package devoted to the application of the Debye function analysis of powder diffraction data from nanocrystalline, defective and/or nonperiodic materials. The general strategy of the suite remains unchanged, following a two-step approach managed by theCLAUDEandDEBUSSYprograms, respectively. The first step essentially consists in generating a database where structural, size and shape information on a nanocrystal population is stored; the second step consists in the calculation, through the Debye scattering equation, of the total diffraction pattern using the previously generated database and a set of model parameters provided by the user and then optimized by the program. The novelties lie in the computational, modelling and graphical levels, and several new programs and features have been added. Among these are a new general comprehensive input file format (.ddb) for the database generation, the automatic management of the space-group symmetry and .cif file, new nanocrystal shapes, size-dependent site occupancy factors and thermal parameters for each atomic species, new lattice expansion functions, and a newly developed algorithm for calculating the standard errors of the optimized parameters. TheCLAUDEsuite also includes a program for calculation of the pair distribution function. Last but not least, a graphical user interface, which makes it easier to edit input files, execute the programs of the suite in a chain-like way, and plot the results in an automatic or custom manner, is provided.

scholarly journals Quantitative modeling of regular retinal microglia distribution

2021 ◽  
Author(s):  
Yoshie Endo ◽  
Daisuke Asanuma ◽  
Shigeyuki Namiki ◽  
Kenzo Hirose ◽  
Akiyoshi Uemura ◽  
...  
Keyword(s):  
Model Simulation ◽  
Cell Movement ◽  
Cell Contact ◽  
Model Parameters ◽  
Regular Distribution ◽  
Cell Spacing ◽  
Process Formation ◽  
Direct Cell ◽  
The Central Nervous System ◽  
Processing Techniques

Microglia are resident immune cells in the central nervous system (CNS), showing a regular distribution. Advancing microscopy and image processing techniques have contributed to elucidating microglia’s morphology, dynamics, and distribution. However, the mechanism underlying the regular distribution of microglia remains to be elucidated. First, we quantitatively confirmed the regularity of the distribution pattern of microglial soma. Second, we formulated a mathematical model that includes factors that may influence regular distribution. Next, we experimentally quantified the model parameters (cell movement, process formation, and ATP dynamics). The resulting model simulation from the measured parameters showed that direct cell-cell contact is most important in generating regular cell spacing. Finally, we tried to specify the molecular pathway responsible for the repulsion between neighboring microglia.

scholarly journals Tissue self-organization based on collective cell migration by contact activation of locomotion and chemotaxis

2019 ◽  
Vol 116 (10) ◽  
pp. 4291-4296 ◽  
Author(s):  
Taihei Fujimori ◽  
Akihiko Nakajima ◽  
Nao Shimada ◽  
Satoshi Sawai
Keyword(s):  
Cell Migration ◽  
Cell Movement ◽  
Tissue Level ◽  
Cell Contact ◽  
Collective Cell Migration ◽  
Contact Activation ◽  
Membrane Recruitment ◽  
Cell Rearrangement ◽  
Cell Protrusion ◽  
Cell Cell

Despite their central role in multicellular organization, navigation rules that dictate cell rearrangement remain largely undefined. Contact between neighboring cells and diffusive attractant molecules are two of the major determinants of tissue-level patterning; however, in most cases, molecular and developmental complexity hinders one from decoding the exact governing rules of individual cell movement. A primordial example of tissue patterning by cell rearrangement is found in the social amoebaDictyostelium discoideumwhere the organizing center or the “tip” self-organizes as a result of sorting of differentiating prestalk and prespore cells. By employing microfluidics and microsphere-based manipulation of navigational cues at the single-cell level, here we uncovered a previously overlooked mode ofDictyosteliumcell migration that is strictly directed by cell–cell contact. The cell–cell contact signal is mediated by E-set Ig-like domain-containing heterophilic adhesion molecules TgrB1/TgrC1 that act in trans to induce plasma membrane recruitment of the SCAR complex and formation of dendritic actin networks, and the resulting cell protrusion competes with those induced by chemoattractant cAMP. Furthermore, we demonstrate that both prestalk and prespore cells can protrude toward the contact signal as well as to chemotax toward cAMP; however, when given both signals, prestalk cells orient toward the chemoattractant, whereas prespore cells choose the contact signal. These data suggest a model of cell sorting by competing juxtacrine and diffusive cues, each with potential to drive its own mode of collective cell migration.

scholarly journals Intermediate adhesion maximizes fluidity and migration velocity of multicellular clusters

2020 ◽  
Author(s):  
U. Roy ◽  
A. Mugler
Keyword(s):  
Cell Adhesion ◽  
Cancer Metastasis ◽  
Lattice Gas ◽  
Migration Velocity ◽  
Cell Contact ◽  
Intermediate Cell ◽  
Two Dimensional ◽  
Dimensional Model ◽  
Loose Packing ◽  
Cell Cell

ABSTRACTCollections of cells exhibit coherent migration during morphogenesis, cancer metastasis, and wound healing. In many cases, bigger clusters split, smaller sub-clusters collide and reassemble, and gaps continually emerge. The connections between cell-level adhesion and cluster-level dynamics, as well as the resulting consequences for cluster properties such as migration velocity, remain poorly understood. Here we investigate collective migration of one- and two-dimensional cell clusters that collectively track chemical gradients using a mechanism based on contact inhibition of locomotion. We develop both a minimal description based on the lattice gas model of statistical physics, and a more realistic framework based on the cellular Potts model which captures cell shape changes and cluster rearrangement. In both cases, we find that cells have an optimal adhesion strength that maximizes cluster migration speed. The optimum negotiates a tradeoff between maintaining cell-cell contact and maintaining cluster fluidity, and we identify maximal variability in the cluster aspect ratio as a revealing signature. Our results suggest a collective benefit for intermediate cell-cell adhesion.SIGNIFICANCECells have been observed to migrate faster and more efficiently in clusters than as individuals. We conjecture that adhesion among cells and with the extracellular environment plays an important role in achieving higher-speed for the entire cluster. We carry out our analyses analytically and computationally, by employing a simplistic one-dimensional model and a realistic two-dimensional model which capture the essential features of multicellular migration. Our study demonstrates that an optimal cell-cell adhesion, which corresponds to maximal cellular rearrangement and loose packing, leads to a higher migration velocity for a multicellular cluster, acting as a crucial factor in effective movement of a collection of cells in a coordinated and directed fashion.

scholarly journals Contact-dependent promotion of cell migration by the OL-protocadherin–Nap1 interaction

2008 ◽  
Vol 182 (2) ◽  
pp. 395-410 ◽  
Author(s):  
Shinsuke Nakao ◽  
Anna Platek ◽  
Shinji Hirano ◽  
Masatoshi Takeichi
Keyword(s):  
Transmembrane Protein ◽  
Cell Movement ◽  
Cell Junctions ◽  
Cell Contact ◽  
Actin Assembly ◽  
Exogenous Expression ◽  
Migration Of Cells ◽  
Cadherin Superfamily ◽  
U251 Cells ◽  
Cell Cell

OL-protocadherin (OL-pc) is a transmembrane protein belonging to the cadherin superfamily, which has been shown to accumulate at cell–cell contacts via its homophilic interaction, but its molecular roles remain elusive. In this study, we show that OL-pc bound Nck-associated protein 1 (Nap1), a protein that regulates WAVE-mediated actin assembly. In astrocytoma U251 cells not expressing OL-pc, Nap1 was localized only along the lamellipodia. However, exogenous expression of OL-pc in these cells recruited Nap1 as well as WAVE1 to cell–cell contact sites. Although OL-pc expression had no effect on the motility of solitary U251 cells, it accelerated their movement when they were in contact with one another, causing concomitant reorganization of F-actin and N-cadherin at cell junctions. OL-pc mutants lacking the Nap1-binding site exhibited no such effect. N-cadherin knockdown mimicked OL-pc expression in enhancing cell movement. These results suggest that OL-pc remodels the motility and adhesion machinery at cell junctions by recruiting the Nap1–WAVE1 complex to these sites and, in turn, promotes the migration of cells.

scholarly journals Correction: Inhibition of cell movement and proliferation by cell–cell contact-induced interaction of Necl-5 with nectin-3

2020 ◽  
Vol 219 (6) ◽  
Author(s):  
Tsutomu Fujito ◽  
Wataru Ikeda ◽  
Shigeki Kakunaga ◽  
Yukiko Minami ◽  
Mihoko Kajita ◽  
...  
Keyword(s):  
Cell Movement ◽  
Cell Contact ◽  
Cell Cell

scholarly journals Tissue self-organization based on collective cell migration by contact activation of locomotion and chemotaxis

2018 ◽  
Author(s):  
Taihei Fujimori ◽  
Akihiko Nakajima ◽  
Nao Shimada ◽  
Satoshi Sawai
Keyword(s):  
Cell Migration ◽  
Individual Cell ◽  
Cell Movement ◽  
Tissue Level ◽  
Cell Contact ◽  
Collective Cell Migration ◽  
Contact Activation ◽  
Cell Rearrangement ◽  
Cell Protrusion ◽  
Cell Cell

AbstractDespite their central role in multicellular organization, navigation rules that dictate cell rearrangement remain much to be elucidated. Contact between neighboring cells and diffusive attractant molecules are two of the major determinants of tissue-level patterning, however in most cases, molecular and developmental complexity hinders one from decoding the exact governing rules of individual cell movement. A primordial example of tissue patterning by cell rearrangement is found in the social amoeba Dictyostelium discoideum where the organizing center or the ‘tip’ self-organize as a result of sorting of differentiating prestalk and prespore cells. Due to its relatively simple and conditional multicellularity, the system provides a rare case where the process can be fully dissected into individual cell behavior. By employing microfluidics and microsphere-based manipulation of navigational cues at the single-cell level, here we uncovered a previously overlooked mode of Dictyostelium cell migration that is strictly directed by cell-cell contact. The cell-cell contact signal is mediated by E-set Ig-like domain containing heterophilic adhesion molecules TgrB1/TgrC1 that act in trans to induce plasma membrane recruitment of SCAR complex and formation of dendritic actin networks, and the resulting cell protrusion competes with those induced by chemoattractant cAMP. Furthermore, we demonstrate that both prestalk and prespore cells can protrude towards the contact signal as well as to chemotax towards cAMP, however when given both signals, prestalk cells orient towards the chemoattractant whereas prespore cells choose the contact signal. These data suggest a new model of cell sorting by competing juxtacrine and diffusive cues each with potential to drive its own mode of collective cell migration. The present findings not only resolve the long standing question of how cells sort in Dictyostelium but also cast light on the remarkable parallels in collective cell migration that evolved independently in metazoa and amoebozoa.

Elevated protein tyrosine phosphatase activity provokes Eph/ephrin-facilitated adhesion of pre-B leukemia cells

Blood ◽  
2008 ◽  
Vol 112 (3) ◽  
pp. 721-732 ◽  
Author(s):  
Sabine H. Wimmer-Kleikamp ◽  
Eva Nievergall ◽  
Kristina Gegenbauer ◽  
Samantha Adikari ◽  
Mariam Mansour ◽  
...  
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Lymphoblastic Leukemia ◽  
Tyrosine Phosphatase ◽  
Cell Movement ◽  
Leukemia Cells ◽  
Cell Contact ◽  
Eph Receptors ◽  
Protein Tyrosine ◽  
Phosphotyrosine Signaling ◽  
Cell Cell

Abstract Signaling by Eph receptors and cell-surface ephrin ligands modulates adhesive cell properties and thereby coordinates cell movement and positioning in normal and oncogenic development. While cell contact–dependent Eph activation frequently leads to cell-cell repulsion, also the diametrically opposite response, cell-cell adhesion, is a probable outcome. However, the molecular principles regulating such disparate functions have remained controversial. We have examined cell-biologic mechanisms underlying this switch by analyzing ephrin-A5–induced cell-morphologic changes of EphA3-positive LK63 pre-B acute lymphoblastic leukemia cells. Their exposure to ephrin-A5 surfaces leads to a rapid conversion from a suspended/nonpolarized to an adherent/polarized cell type, a transition that relies on EphA3 functions operating in the absence of Eph-kinase signaling. Cell morphology change and adhesion of LK63 cells are effectively attenuated by endogenous protein tyrosine phosphatase (PTP) activity, whereby PTP inhibition and productive EphA3-phosphotyrosine signaling reverse the phenotype to nonadherent cells with a condensed cytoskeleton. Our findings suggest that Eph-associated PTP activities not only control receptor phosphorylation levels, but as a result switch the response to ephrin contact from repulsion to adhesion, which may play a role in the pathology of hematopoietic tumors.

scholarly journals Inhibition of cell movement and proliferation by cell–cell contact-induced interaction of Necl-5 with nectin-3

2005 ◽  
Vol 171 (1) ◽  
pp. 165-173 ◽  
Author(s):  
Tsutomu Fujito ◽  
Wataru Ikeda ◽  
Shigeki Kakunaga ◽  
Yukiko Minami ◽  
Mihoko Kajita ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Adhesion Molecule ◽  
Cell Movement ◽  
Cell Contact ◽  
Down Regulation ◽  
Nih3t3 Cells ◽  
Cell Contacts ◽  
Poliovirus Receptor ◽  
A Cell ◽  
Cell Cell

Immunoglobulin-like Necl-5/Tage4/poliovirus receptor (PVR)/CD155, originally identified as the PVR, has been shown to be up-regulated in cancer cells and to enhance growth factor–induced cell movement and proliferation. In addition, Necl-5 heterophilically trans-interacts with nectin-3, a cell–cell adhesion molecule known to form adherens junctions in cooperation with cadherin. We show here that Necl-5 was down-regulated from cell surface upon cell–cell contacts in NIH3T3 cells. This down-regulation of Necl-5 was initiated by its interaction with nectin-3 and was mainly mediated by clathrin-dependent endocytosis. Then, the down-regulation of Necl-5 induced in this way reduced movement and proliferation of NIH3T3 cells. These results indicate that the down-regulation of Necl-5 induced by its interaction with nectin-3 upon cell–cell contacts may be at least one mechanism underlying contact inhibition of cell movement and proliferation.

Sign in / Sign up

Export Citation Format

Share Document