Utilisateur:Saksihw/Brouillon2

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La migration cellulaire est un processus central dans le developpement et la maintenance des organismes multicellulaires. Formation des tissus pendant le developpement embryonnaire, cicatrisation, reponse immunitaire, metastase et invasion cancereuse, etablissement des connections neuronales requierent tous le mouvement orchestre de cellules, parfois dans des directions particulieres ou a des endroits particuliers. Les cellules migrent souvent en reponse a des signaux externes specifiques, comme les signaux chimiotactiques ou mecanotactiques. Due a l'environnement hautement visqueux (faible nombre de Reynolds) qu'elles rencontrent, les cellules produisent en permanence des forces mecaniques pour se mouvoir. Les cellules effectuent un mouvement actif grace a des mecanismes tres differents. Les organismes procaryotes (et les spermatozoides) utilisent des flagelles ou des cils pour se propulser. La migration eucaryote est largement plus complexe et peut consister en la combination de differents mecanismes migratoires. Two very distinct migration scenarios are crawling motion (most commonly studied) and blebbing motility.[1]

Cela implique generalement la mise en place d'une polarisation antero-posterieure, une modification de la dynamique membranaire et des changements drastiques de la morphologie de la cellule. Cette reorganisation dynamique de la cellule repose en tres grande partie sur son cytosquelette. Detection des signaux pro-migratoire, polarisation, generation des forces mecaniques, reorganisation du cytosquelette et de la morphologie necessite un grand nombre de voies de signalisation moleculaires. Ainsi, compte-tenu de la complexite de sa complexite et de son ubiquite, la migration cellulaire est un champs d'investigation majeur de la mecanobiologie et de la biologie cellulaire et moleculaire actuelle.


Des defauts de ce phenomene ont des consequences lourdes, incluant le retard mental, les maladies cardiovasculaires, le cancer, les immunodeficiences. intellectual disability, vascular disease, tumor formation and metastasis. De ce fait, sa comprehension et sa maitrise represente des enjeux biomedicaux importants. 

Cells often migrate in response to specific external signals, including chemical signals and mechanical signals.


Etudes de la migration cellulaires[modifier | modifier le code]

Figure 1: A Time-lapse microscopy video of migrating MCF-10A cells, imaged for 16 hours using quantitative phase microscopy.[2]

La migration de cellules en culture attachees a une surface est generalement etudiee par microscopie. Le mouvement cellulaire etant lent (quelque um/minute) des videos sont enregistrees (time-lapse microscopy) des cellules en migration afin d'accelerer le mouvement. De telles videos (Figure 1) montre que le front avant de la cellule est tres actif, avec un comportement caracteristique de contractions et expansions successives. Il est generalement accepte que le front avant est le moteur principal qui tire la cellule vers l'avant.

Caracteristiques communes[modifier | modifier le code]

Les processus sous-jascents de la migration des cellules de mammiferes sont consideres comme etant similaires a ceux du mouvement amiboide (hormis le mouvement des spermatozoides). [3] Observations in common include: Les points communs incluent:

  • Deplacement du cytoplasme au bord anterieur (front)
  • Evacuation laminaire des debris accumules en position dorsale vers le bord posterieur (arriere.

Cette derniere caracteristique est plus facilement observee quand les aggregats d'une molecule de surface sont fixes avec un anticorps fluorescent ou auqnd de petites billes sont artificiellement fixees au front avant de la cellule.[4]

D'autres cellules eucaryotes migrent de la meme maniere. L'amibe Dictyostelium discoideum est un modele de recherche utile car il adopte systematiquement un comportement chimiotactique en repose a l'Adenosine MonoPhosphate cyclique. Il bouge plus rapidement que les cellules mammaliennes en culture et leur genome haploide facilite les etudes genetiques visant a relier un gene particulier a un effet sur le comportement cellulaire.

Deux modeles differents de la migration cellulaires A) modele cytosqueletique. B) Modele du flux membranaire
(A) Des microtubules dynamiques sont necessaire pour la retractation de la queue et sont repartis a l'arriere de la cellule en migration. Vert, microtubules hautement dynamiques, jaune, microtubules moderement dynamiques, rouge microtubule stable. Green, highly dynamic microtubules; yellow, moderately dynamic microtubules and red, stable microtubules. (B) Microtubules stables agissent comme support et previennent une retractation de la queue et inhibent de facto la migration cellulaire.

Molecular processes of migration[modifier | modifier le code]

There are two main theories for how the cell advances its front edge: the cytoskeletal model and membrane flow model. It is possible that both underlying processes contribute to cell extension.

Cytoskeletal model (A)[modifier | modifier le code]

Leading Edge[modifier | modifier le code]

Experimentation has shown that there is rapid actin polymerisation at the cell's front edge.[5] This observation has led to the hypothesis that formation of actin filaments "push" the leading edge forward and is the main motile force for advancing the cell’s front edge.[6][7] In addition, cytoskeletal elements are able to interact extensively and intimately with a cell's plasma membrane.[8]

Trailing Edge[modifier | modifier le code]

Other cytoskeletal components (like microtubules) have important functions in cell migration. It has been found that microtubules act as “struts” that counteract the contractile forces that are needed for trailing edge retraction during cell movement. When microtubules in the trailing edge of cell are dynamic, they are able to remodel to allow retraction. When dynamics are suppressed, microtubules cannot remodel and, therefore, oppose the contractile forces.[9] The morphology of cells with suppressed microtubule dynamics indicate that cells can extended the front edge (polarized in the direction of movement), but have difficulty retracting their trailing edge.[10] On the other hand high drug concentrations, or microtubule mutations that depolymerize the microtubules, can restore cell migration but there is a loss of directionality. It can be concluded that microtubules act both to restrain cell movement and to establish directionality.

Membrane flow model (B)[modifier | modifier le code]

Studies have also shown that the front is the site at which membrane is returned to the cell surface from internal membrane pools at the end of the endocytic cycle.[11] This has led to the hypothesis that extension of the leading edge occurs primarily by addition of membrane at the front of the cell. If so, the actin filaments that form at the front might stabilize the added membrane so that a structured extension, or lamella, is formed rather than a bubble-like structure (or bleb) at its front.[12] For a cell to move, it is necessary to bring a fresh supply of "feet" (proteins called integrins, which attach a cell to the surface on which it is crawling) to the front. It is likely that these feet are endocytosed toward the rear of the cell and brought to the cell's front by exocytosis, to be reused to form new attachments to the substrate.

Fichier:Collective Mechanism of Cell Motion.jpg
Schematic representation of the collective biomechanical and molecular mechanism of cell motion

Collective biomechanical and molecular mechanism of cell motion[modifier | modifier le code]

Based on some mathematical models recent studies hypothesize a novel biological model for collective biomechanical and molecular mechanism of cell motion.[13] It is proposed that microdomains weave the texture of cytoskeleton and their interactions mark the location for formation of new adhesion sites. According to this model microdomain signaling dynamics organizes cytoskeleton and its interaction with substratum. As microdomains trigger and maintain active polymerization of actin filaments, their propagation and zigzagging motion on the membrane generate a highly interlinked network of curved or linear filaments oriented at a wide spectrum of angles to the cell boundary. It is also proposed that microdomain interaction marks the formation of new focal adhesion sites at the cell periphery. Myosin interaction with the actin network then generate membrane retraction/ruffling, retrograde flow, and contractile forces for forward motion. Finally, continuous application of stress on the old focal adhesion sites could result in the calcium-induced calpain activation, and consequently the detachment of focal adhesions which completes the cycle.

Polarity in migrating cells[modifier | modifier le code]

Migrating cells have a polarity—a front and a back. Without it, they would move in all directions at once, i.e. spread. How this arrow is formulated at a molecular level inside a cell is unknown. In a cell that is meandering in a random way, the front can easily give way to become passive as some other region, or regions, of the cell form(s) a new front. In chemotaxing cells, the stability of the front appears enhanced as the cell advances toward a higher concentration of the stimulating chemical. This polarity is reflected at a molecular level by a restriction of certain molecules to particular regions of the inner cell surface. Thus, the phospholipid PIP3 and activated Rac and CDC42 are found at the front of the cell, whereas Rho GTPase and PTEN are found toward the rear.[14][15]

It is believed that filamentous actins and microtubules are important for establishing and maintaining a cell’s polarity. Drugs that destroy actin filaments have multiple and complex effects, reflecting the wide role that these filaments play in many cell processes. It may be that, as part of the locomotory process, membrane vesicles are transported along these filaments to the cell’s front. In chemotaxing cells, the increased persistence of migration toward the target may result from an increased stability of the arrangement of the filamentous structures inside the cell and determine its polarity. In turn, these filamentous structures may be arranged inside the cell according to how molecules like PIP3 and PTEN are arranged on the inner cell membrane. And where these are located appears in turn to be determined by the chemoattractant signals as these impinge on specific receptors on the cell’s outer surface.

Although microtubules have been known to influence cell migration for many years, the mechanism by which they do so has remained controversial. On a planar surface, microtubules are not needed for the movement, but they are required to provide directionality to cell movement and efficient protrusion of the leading edge.[10][16] When present, microtubules retard cell movement when their dynamics are suppressed by drug treatment or by tubulin mutations.[10]

See also[modifier | modifier le code]

Modèle:Portal

External links[modifier | modifier le code]

References[modifier | modifier le code]

  1. ↑ F Huber, J Schnauss, S Roenicke, P Rauch, K Mueller, C Fuetterer et J Kaes, « Emergent complexity of the cytoskeleton: from single filaments to tissue », Advances in Physics, vol. 62, no 1,‎ , p. 1–112 (PMID 24748680, DOI 10.1080/00018732.2013.771509) online
  2. ↑ « HoloMonitor - Non-invasive image cytometers », Phase Holographic Imaging AB
  3. ↑ « What is Cell Migration? », Cell Migration Gateway, Cell MIgration Consortium (consulté le )
  4. ↑ M Abercrombie, JE Heaysman et SM Pegrum, « The locomotion of fibroblasts in culture III. Movements of particles on the dorsal surface of the leading lamella », Experimental Cell Research, vol. 62, no 2,‎ , p. 389–98 (PMID 5531377, DOI 10.1016/0014-4827(70)90570-7)
  5. ↑ Y. L. Wang, « Exchange of actin subunits at the leading edge of living fibroblasts: possible role of treadmilling », The Journal of Cell Biology, vol. 101, no 2,‎ , p. 597–602 (PMID 4040521, PMCID 2113673, DOI 10.1083/jcb.101.2.597)
  6. ↑ T Mitchison et LP Cramer, « Actin-Based Cell Motility and Cell Locomotion », Cell, vol. 84, no 3,‎ , p. 371–9 (PMID 8608590, DOI 10.1016/S0092-8674(00)81281-7)
  7. ↑ Thomas D Pollard et Gary G Borisy, « Cellular Motility Driven by Assembly and Disassembly of Actin Filaments », Cell, vol. 112, no 4,‎ , p. 453–65 (PMID 12600310, DOI 10.1016/S0092-8674(03)00120-X)
  8. ↑ Gary J. Doherty et Harvey T. McMahon, « Mediation, Modulation, and Consequences of Membrane-Cytoskeleton Interactions », Annual Review of Biophysics, vol. 37,‎ , p. 65–95 (PMID 18573073, DOI 10.1146/annurev.biophys.37.032807.125912)
  9. ↑ Hailing Yang, Anutosh Ganguly et Fernando Cabral, « Inhibition of Cell Migration and Cell Division Correlates with Distinct Effects of Microtubule Inhibiting Drugs », The Journal of Biological Chemistry, vol. 285, no 42,‎ , p. 32242–50 (PMID 20696757, PMCID 2952225, DOI 10.1074/jbc.M110.160820)
  10. ↑ a b et c A Ganguly, H Yang, R Sharma, K Patel et F Cabral, « The Role of Microtubules and Their Dynamics in Cell Migration. », J Biol Chem., vol. 4, no 52,‎ , p. 253–65 (PMID 23135278, DOI 10.1074/jbc.M112.423905)
  11. ↑ M. S. Bretscher, « Distribution of receptors for transferrin and low density lipoprotein on the surface of giant HeLa cells », Proceedings of the National Academy of Sciences, vol. 80, no 2,‎ , p. 454–8 (PMID 6300844, PMCID 393396, DOI 10.1073/pnas.80.2.454)
  12. ↑ M Bretscher, « Getting Membrane Flow and the Cytoskeleton to Cooperate in Moving Cells », Cell, vol. 87, no 4,‎ , p. 601–6 (PMID 8929529, DOI 10.1016/S0092-8674(00)81380-X)
  13. ↑ Hasan Coskun et Huseyin. Coskun, « Cell physician: reading cell motion. A mathematical diagnostic technique through analysis of single cell motion », Bull Math Biol, vol. 73, no 3,‎ , p. 658-82 (DOI 10.1007/s11538-010-9580-x, lire en ligne)
  14. ↑ C. A. Parent et PN Devreotes, « A Cell's Sense of Direction », Science, vol. 284, no 5415,‎ , p. 765–70 (PMID 10221901, DOI 10.1126/science.284.5415.765)
  15. ↑ A. J. Ridley, MA Schwartz, K Burridge, RA Firtel, MH Ginsberg, G Borisy, JT Parsons et AR Horwitz, « Cell Migration: Integrating Signals from Front to Back », Science, vol. 302, no 5651,‎ , p. 1704–9 (PMID 14657486, DOI 10.1126/science.1092053)
  16. ↑ A.S. Meyer, S.K. Hughes-Alford, J.E. Kay, A. Castillo, A. Wells, F.B. Gertler et D.A. Lauffenburger, « 2D protrusion but not motility predicts growth factor–induced cancer cell migration in 3D collagen », J Cell Biol., vol. 194, no 6,‎ , p. 721–729 (PMID 22665521, PMCID 3373410, DOI 10.1083/jcb.201201003)
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