scholarly journals Bursts of activity in collective cell migration

2016 ◽  
Vol 113 (41) ◽  
pp. 11408-11413 ◽  
Author(s):  
Oleksandr Chepizhko ◽  
Costanza Giampietro ◽  
Eleonora Mastrapasqua ◽  
Mehdi Nourazar ◽  
Miriam Ascagni ◽  
...  
Keyword(s):  
Cell Migration ◽  
Scaling Laws ◽  
Domain Walls ◽  
Collective Motion ◽  
Cell Types ◽  
Living Cells ◽  
Collective Cell Migration ◽  
Relaxation Dynamics ◽  
Active Particles ◽  
Different Cell Types

Dense monolayers of living cells display intriguing relaxation dynamics, reminiscent of soft and glassy materials close to the jamming transition, and migrate collectively when space is available, as in wound healing or in cancer invasion. Here we show that collective cell migration occurs in bursts that are similar to those recorded in the propagation of cracks, fluid fronts in porous media, and ferromagnetic domain walls. In analogy with these systems, the distribution of activity bursts displays scaling laws that are universal in different cell types and for cells moving on different substrates. The main features of the invasion dynamics are quantitatively captured by a model of interacting active particles moving in a disordered landscape. Our results illustrate that collective motion of living cells is analogous to the corresponding dynamics in driven, but inanimate, systems.

scholarly journals The Influence of Structural Gradients in Large Pore Organosilica Materials on the Capabilities for Hosting Cellular Communities

2020 ◽  
Author(s):  
Hannah Bronner ◽  
Anna-Katharina Holzer ◽  
Alexander Finke ◽  
Marius Kunkel ◽  
Andreas Marx ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Special Property ◽  
Cell Types ◽  
Living Cells ◽  
Biological Processes ◽  
Native State ◽  
Chemical Gradient ◽  
Polymeric Foam ◽  
Different Cell Types ◽  
Organosilica Materials

<div><div><div><div><p>Cells exist in the so-called extracellular matrix (ECM) in their native state, and numerous future applications require reliable and potent ECM-mimics. A perspective, which goes beyond ECM emulation, is the design of a host-material with features, which are not accessible in the biological portfolio. Such a feature would, for instance be, the creation of a structural or chemical gradient, and to explore how this special property influences the biological processes. First, we wanted to test if macroporous organosilica materials with appropriate surface modification can act as a host for the implementation of human cells like HeLa or LUHMES. It was possible to use a commercially available polymeric foam as a scaffold and coat it with a layer of a thiophenol-containing organosilica layer, followed by biofunctionalization with biotin using click chemistry and the subsequent coupling of streptavidin - fibronectin to it. More importantly, deformation of the scaffold allowed the generation of a permanent structural gradient. In this work, we show that the structural gradient has a tremendous influence on the capability of the described material for the accommodation of living cells. The introduction of a bi-directional gradient enabled the establishment of a cellular community comprising different cell types in spatially distinct regions of the material. An interesting perspective is to study communication between cell types or to create cellular communities, which can never exist in a natural enviornment.</p></div></div></div></div>

THE TRANSLATION OF MESSENGER RNA INJECTED IN LIVING OOCYTES OF XENOPUS LAEVIS

1973 ◽  
Vol 74 (Suppl) ◽  
pp. S225-S243 ◽  
Author(s):  
J. B. Gurdon
Keyword(s):  
Xenopus Laevis ◽  
Messenger Rna ◽  
Cell Types ◽  
Living Cells ◽  
Cell Component ◽  
Globin Mrna ◽  
Spare Capacity ◽  
Specific Component ◽  
Lower Efficiency ◽  
Different Cell Types

ABSTRACT Messenger RNA (mRNA) can be injected in known quantities into oocytes of the frog Xenopus laevis. Haemoglobin mRNA from rabbit, mouse, or duck blood cells is accurately translated, and oocytes can translate messages from different cell-types of all vertebrate groups. Oocytes and eggs have a spare capacity to translate injected messages, even when supplied in excess, and these do not compete with the cells' own messages already in use. The cell component which restricts the translation of injected mRNA above a saturating amount appears not to be KCl-released ribosome factors or transfer RNA. A message-specific component may be responsible for the lower efficiency of translation of α than of β globin mRNA in oocytes. Injected haemoglobin mRNA appears to be translated less frequently in oocytes than in reticulocytes at the same temperature, but continues to be translated in oocytes at nearly the same rate for a period of up to nearly 2 weeks. The injection of mRNA into oocytes is especially valuable for studying the control of protein synthesis in living cells.

scholarly journals Tousled-like kinase regulates cytokine-mediated communication between cooperating cell types during collective border cell migration

2016 ◽  
Vol 27 (1) ◽  
pp. 12-19 ◽  
Author(s):  
Wenjuan Xiang ◽  
Dabing Zhang ◽  
Denise J. Montell
Keyword(s):  
Cell Migration ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Metastatic Cancer ◽  
Cell Types ◽  
Collective Cell Migration ◽  
Border Cells ◽  
Border Cell ◽  
Stat Signaling ◽  
Border Cell Migration

Collective cell migration is emerging as a major contributor to normal development and disease. Collective movement of border cells in the Drosophila ovary requires cooperation between two distinct cell types: four to six migratory cells surrounding two immotile cells called polar cells. Polar cells secrete a cytokine, Unpaired (Upd), which activates JAK/STAT signaling in neighboring cells, stimulating their motility. Without Upd, migration fails, causing sterility. Ectopic Upd expression is sufficient to stimulate motility in otherwise immobile cells. Thus regulation of Upd is key. Here we report a limited RNAi screen for nuclear proteins required for border cell migration, which revealed that the gene encoding Tousled-like kinase (Tlk) is required in polar cells for Upd expression without affecting polar cell fate. In the absence of Tlk, fewer border cells are recruited and motility is impaired, similar to inhibition of JAK/STAT signaling. We further show that Tlk in polar cells is required for JAK/STAT activation in border cells. Genetic interactions further confirmed Tlk as a new regulator of Upd/JAK/STAT signaling. These findings shed light on the molecular mechanisms regulating the cooperation of motile and nonmotile cells during collective invasion, a phenomenon that may also drive metastatic cancer.

scholarly journals Mesenchymal stem cells carry and transport clusters of cancer cells

2021 ◽  
Author(s):  
Jana Zarubova ◽  
Mohammad Mahdi Hasani-Sadrabadi ◽  
Sam CP Norris ◽  
Andrea M Kasko ◽  
Song Li
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Migration ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Cell Types ◽  
Cell Clusters ◽  
Different Cell Types

AbstractCell clusters that collectively migrate from primary tumors appear to be far more potent in forming distant metastases than single cancer cells. A better understanding of collective cell migration phenomenon and the involvement of different cell types during this process is needed. Here, we utilize a micropatterned surface composed of a thousand of low-adhesive microwells to screen motility of spheroids containing different cell types by analyzing their ability to move from the bottom to the top of the microwells. Mesenchymal stem cells (MSCs) spheroid migration was efficient in contrast to cancer cell only spheroids. In spheroids with both cell types mixed together, MSCs were able to carry the low-motile cancer cells during migration. As the percentage of MSCs increased in the spheroids, more migrating spheroids were detected. Extracellular vesicles secreted by MSCs also contributed to the pro-migratory effect exerted by MSCs. However, the transport of cancer cells was more efficient when MSCs were physically present in the cluster. Similar results were obtained when cell clusters were encapsulated within a micropatterned hydrogel, where collective migration was guided by micropatterned matrix stiffness. These results suggest that stromal cells facilitate the migration of cancer cell clusters, which is contrary to the general belief that malignant cells metastasize independently.SignificanceDuring metastasis, tumor cells may migrate as a cluster, which exhibit higher metastatic capacity compared to single cells. However, whether and how non-cancer cells contained in tumor cluster regulate it’s migration is not clear. Here, we utilize two unique approaches to study collective tumor cell migration in vitro: first, in low-adhesive microwells and second, in micropatterned hydrogels to analyze migration in 3D microenvironment. Our results indicate that MSCs in tumor cell clusters could play an important role in the dissemination of cancer cells by actively transporting low-motile cancer cells. In addition, MSC-released paracrine factors also increase the motility of tumor cells. These findings reveal a new mechanism of cancer cell migration and may lead to new approaches to suppress metastases.

scholarly journals Multiscale modelling of motility wave propagation in cell migration

2020 ◽  
Author(s):  
Hamid Khatee ◽  
Andras Czirok ◽  
Zoltan Neufeld
Keyword(s):  
Cell Migration ◽  
Collective Motion ◽  
Leading Edge ◽  
Collective Cell Migration ◽  
Tissue Formation ◽  
Cell Monolayers ◽  
Polarization Wave ◽  
Fundamental Biological Process ◽  
Cortical Contractility ◽  
Contractile Cells

AbstractThe collective motion of cell monolayers within a tissue is a fundamental biological process that occurs during tissue formation, wound healing, cancerous invasion, and viral infection. Experiments have shown that at the onset of migration, the motility is self-generated as a polarization wave starting from the leading edge of the monolayer and progressively propagates into the bulk. However, it is unclear how the propagation of this motility wave is influenced by cellular properties. Here, we investigate this using a computational model based on the Potts model coupled to the dynamics of intracellular polarization. The model captures the propagation of the polarization wave initiated at the leading edge and suggests that the cells cortex can regulate the migration modes: strongly contractile cells may depolarize the monolayer, whereas less contractile cells can form swirling movement. Cortical contractility is further found to limit the cells motility, which (i) decelerates the wave speed and the leading edge progression, and (ii) destabilises the leading edge into migration fingers. Together, our model describes how different cellular properties can contribute to the regulation of collective cell migration.

Proteolytic and non-proteolytic migration of tumour cells and leucocytes

2003 ◽  
Vol 70 ◽  
pp. 277-285 ◽  
Author(s):  
Peter Friedl ◽  
Katarina Wolf
Keyword(s):  
Cell Migration ◽  
Matrix Metalloproteinases ◽  
Shape Change ◽  
Imaging Techniques ◽  
Three Dimensional ◽  
Cell Types ◽  
Cysteine Proteases ◽  
Tumour Cells ◽  
Amoeboid Movement ◽  
Different Cell Types

The migration of different cell types, such as leucocytes and tumour cells, involves cellular strategies to overcome the physical resistance of three-dimensional tissue networks, including proteolytic degradation of extracellular matrix (ECM) components. High-resolution live-cell imaging techniques have recently provided structural and biochemical insight into the differential use of matrix-degrading enzymes in the migration processes of different cell types within the three-dimensional ECM. Proteolytic migration is achieved by slow-moving cells, such as fibroblasts and mesenchymally moving tumour cells, by engaging matrix metalloproteinases, cathepsins and serine proteases at the cell surface in a focalized manner ('pericellular proteolysis'), while adhesion and migratory traction are provided by integrins. Pericellular breakdown of ECM components generates localized matrix defects and remodelling along migration tracks. In contrast with tumour cells, constitutive non-proteolytic migration is used by rapidly moving T lymphocytes. This migration type does not generate proteolytic matrix remodelling, but rather depends on shape change to allow cells to glide and squeeze through gaps and trails present in connective tissues. In addition, constitutive proteolytic migration can be converted into non-proteolytic movement by protease inhibitors. After the simultaneous inhibition of matrix metalloproteinases, serine/threonine proteases and cysteine proteases in tumour cells undergoing proteolysis-dependent movement, a fundamental adaptation towards amoeboid movement is able to sustain non-proteolytic migration in these tumour cells (the mesenchymal-amoeboid transition). Instead of using proteases for matrix degradation, the tumour cells use leucoyte-like strategies of shape change and squeezing through matrix gaps along tissue scaffolds. The diversity of protease function in cell migration by different cell types highlights response diversity and molecular adaptation of cell migration upon pharmacotherapeutic protease inhibitor treatment.

scholarly journals PTTG1/securin modulates microtubule nucleation and cell migration

2011 ◽  
Vol 22 (22) ◽  
pp. 4302-4311 ◽  
Author(s):  
Miguel A. Moreno-Mateos ◽  
Águeda G. Espina ◽  
Belén Torres ◽  
María M. Gámez del Estal ◽  
Ana Romero-Franco ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Cell Types ◽  
Cell Polarization ◽  
Biological Functions ◽  
Microtubule Nucleation ◽  
And Migration ◽  
Different Cell Types ◽  
Transforming Gene

Pituitary tumor transforming gene 1 (PTTG1), also known as securin, has been implicated in many biological functions, including inhibition of sister chromatid separation, DNA repair, organ development, and regulation of the expression and secretion of angiogenic and metastatic factors. Although most of these functions of securin seem to depend on the localization of PTTG1 in the nucleus of the cell, a fraction of the protein has been also detected in the cytoplasm. Here we demonstrate that, in different cell types, a portion of cytoplasmic PTTG1 is associated with the cis face of the Golgi apparatus and that this localization depends on PTTG1 phosphorylation status. In this organelle, PTTG1 forms a complex with proteins involved in microtubule nucleation, including GM130, AKAP450, and γ-tubulin. RNA interference–mediated depletion of PTTG1 produces a delay in centrosomal and noncentrosomal microtubule nucleation. Cells lacking PTTG1 show severe defects in both cell polarization and migration in wound-healing assays. To our knowledge, this is the first study reporting the role of PTTG1 in microtubule nucleation and cell polarization, two processes directly involved in cell migration. We believe that these findings will contribute to understanding the mechanisms underlying PTTG1-mediated biological functions.

scholarly journals So Many Plasminogen Receptors: Why?

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Edward F. Plow ◽  
Loic Doeuvre ◽  
Riku Das
Keyword(s):  
Cell Migration ◽  
Protease Activity ◽  
Cellular Response ◽  
Inflammatory Cell ◽  
Cell Types ◽  
Cellular Responses ◽  
Cellular Migration ◽  
Plasminogen Activation ◽  
Cell Surfaces ◽  
Different Cell Types

Plasminogen and plasmin tether to cell surfaces through ubiquitously expressed and structurally quite dissimilar family of proteins, as well as some nonproteins, that are collectively referred to as plasminogen receptors. Of the more than one dozen plasminogen receptors that have been identified, many have been shown to facilitate plasminogen activation to plasmin and to protect bound plasmin from inactivation by inhibitors. The generation of such localized and sustained protease activity is utilized to facilitate numerous cellular responses, including responses that depend on cellular migration. However, many cells express multiple plasminogen receptors and numerous plasminogen receptors are expressed on many different cell types. Furthermore, several different plasminogen receptors can be used to support the same cellular response, such as inflammatory cell migration. Here, we discuss the perplexing issue: why are there so many different Plg-Rs?

scholarly journals Ctdnep1 and Eps8L2 regulate dorsal actin cables for nuclear positioning during cell migration

2020 ◽  
Author(s):  
Francisco J. Calero-Cuenca ◽  
Daniel S. Osorio ◽  
Sreerama Chaitanya Sridhara ◽  
Yue Jiao ◽  
Jheimmy Diaz ◽  
...  
Keyword(s):  
Cell Migration ◽  
Nuclear Envelope ◽  
Leading Edge ◽  
Cell Types ◽  
Linc Complex ◽  
Nuclear Positioning ◽  
Physiological Functions ◽  
Actin Cables ◽  
Different Cell Types

SummaryCells actively position their nuclei within the cytoplasm for multiple cellular and physiological functions. Different cell types position their nuclei away from the leading edge to migrate properly. In migrating fibroblasts, nuclear positioning is driven by dorsal actin cables connected to the nuclear envelope by the LINC complex on Transmembrane Actin-associated Nuclear (TAN) lines. How dorsal actin cables are organized to form TAN lines is unknown. Here, we report a role for Ctdnep1/Dullard, a nuclear envelope phosphatase, and the actin regulator Eps8L2, on nuclear positioning. We demonstrate that Ctdnep1 and Eps8L2 directly interact to regulate the formation and thickness of dorsal actin cables required for TAN lines engagement for nuclear positioning. Our work establishes a novel mechanism to locally regulate actin at the nuclear envelope for nuclear positioning.

scholarly journals A cell-based probabilistic approach unveils the concerted action of miRNAs

2018 ◽  
Author(s):  
Shelly Mahlab-Aviv ◽  
Nathan Linial ◽  
Michal Linial
Keyword(s):  
Cellular Response ◽  
Probabilistic Approach ◽  
Cell Types ◽  
Living Cells ◽  
List Type ◽  
Translation Machinery ◽  
Translational Machinery ◽  
Cooperative Action ◽  
Stochastic Framework ◽  
Different Cell Types

SummaryMature microRNAs (miRNAs) regulate most human genes through direct base-pairing with mRNAs. We investigate some underlying principles of such regulation. To this end, we overexpressed miRNAs in different cell types and measured the mRNA decay rate under transcriptional arrest. Parameters extracted from these experiments were incorporated into a computational stochastic framework which was developed to simulate the cooperative action of miRNAs in living cells. We identified gene sets that exhibit coordinated behavior with respect to all major miRNAs, over a broad range of overexpression levels. While a small set of genes is highly sensitive to miRNA manipulations, about 180 genes are insensitive to miRNA manipulations as measured by their degree of mRNA retention. The insensitive genes are associated with the translation machinery. We conclude that the stochastic nature of miRNAs reveals an unexpected robustness of gene expression in living cells. Moreover, the use of a systematic probabilistic approach exposes design principles of cells’ states and in particular, the translational machinery.HighlightsA probabilistic-based simulator assesses the cellular response to thousands of miRNA overexpression manipulationsThe translational machinery displays an exceptional resistance to manipulations of miRNAs.The insensitivity of the translation machinery to miRNA manipulations is shared by different cell typesThe composition of the most abundant miRNAs dominates cell identity

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