Abstract
While the control of cell migration by biochemical and biophysical factors is largely documented, a precise quantification of cell migration parameters in different experimental contexts is still questionable. Indeed, these phenomenological parameters can be evaluated from data obtained either at the cell population level or at the individual cell level. However, the range within which both characterizations of cell migration are equivalent remains unclear. We analyse here to which extent both sources of data could be integrated within a unified description of cell migration by considering the motility of the endothelial cell line EAhy926. Using time-lapse video-microscopy and associated analysis of digital image time series, we quantified EAhy926 random motility coefficient, migration speed and trajectory persistence time in two different migration assays: the in vitro wound healing assay, and the cell-populated agarose drop assay. In order to analyse the agreement between independent quantifications of cell motility based either on individual cell analysis or cell population dynamic analysis, a theoretical multi-agents cellular model was developed and discussed as a possible theoretical framework able to unify these multi-scale data. Model simulations especially reveal the potential bias induced by cell proliferation and cell-cell adhesion when cell migration parameters are estimated from the extensively used in vitro wound healing assay.
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REFERENCES
Addadi-Rebbah, S., S. Poitevin, N. Fourre, M. Polette, R. Garnotel and P. Jeannesson (2004). Assessment of the antiinvasive potential of the anthracycline aclacinomycin (Aclarubicin) in a human fibrosarcoma cell line. International Journal of Oncology 24: 1607–1615.
Albini, A., C. Marchisone, F. Del Grosso, R. Benelli, L. Masiello, C. Tacchetti, M. Bono, M. Ferrantini, C. Rozera, M. Truini, F. Belardelli, L. Santi and DM. Noonan (2000). Inhibition of angiogenesis and vascular tumor growth by interferon-producing cells: A gene therapy approach. American Journal of pathology 156: 1381–1393.
Benndorf, R., R.H. Boger, S. Ergun, A. Steenpass and T. Wieland (2003). Angiotensin II type 2 receptor inhibits vascular endothelial growth factor-induced migration and in vitro tube formation of human endothelial cells. Circulation Research 93: 438–447.
Bereiter-Hahn, J. and H. Lüers (1994). The role of elasticity in the motile behavior of cells. In: Akkas, N. (Ed.). Biomechanics of active movement and division of cells, NATO AS1 Series. pp 181–229. Springer Verlag, Berlin.
Bergman, A.J. and K. Zygourakis (1999). Migration of lymphocytes on fibronectin-coated surfaces: temporal evolution of migratory parameters. Biomaterials 20: 2235–2224.
Boucher, A., A. Doisy, X. Ronot and C. Garbay (1998). Cell migration analysis after in vitro wounding injury with a multi-agent approach. Artificial Intelligence Review 12: 137–162.
Bouis, D., G. A. Hospers, C. Meijer, G. Molema and N.H. Mulder (2001). Endothelium in vitro: a review of human vascular endothelial cell lines for blood vessel-related research. Angiogenesis 4: 91–102.
Boyden, S.B. (1962). The chemotactic effect of mixtures of antibody and antigen on polymorphonuclear leukocytes. Journal of Experimenta1 Medicine 115: 451–460.
Chen, C.S., J.L. Alonso, E. Ostuni, G.M. Whitesides and D.E. Ingber (2003). Cell shape provides global control of focal adhesion assembly. Biochemical and Biophysical Research Communications 307: 355–61
DiMilla, PA., J.A. Quinn, S.M. Albelda and D.A. Lauffenburger (1992) Measurement of individual cell migration parameters for human tissue cells. AIChE Journal 38: 1092–1 104.
DiMilla, P.A., J.A. Stone, J.A. Quinn, S.M. Albelda and D.A. Lauffenburger (1993) Maximal migration of human smooth muscle cells on fibronectin and type IV collagen occurs at an intermediate attachment strength. Journal of Cell Biology 122: 729–737.
Dickinson. R.B., J.B. McCarthv and R.T. Tranquillo (1993). Quantitative characterization of cell invasion in vitro: formulation and validation of a mathematical model of the collagen gel invasion assay. Annals of Biomechanical Engineering 21: 679–697.
Dugnolle, P., C. Garbay and P. Tracqui (1998). A mechanical model to simulate cell reorganisation during in vitro wound healing, Proceedings ESM'98, "Simulation Tools in Biology". pp. 333–347 SCS Europe, Manchester.
Edgell, C.J., C. C. McDonald and J. B. Graham (1983). Permanent cell line expressing human factor VIII-related antigen established by hybridization. Proceedings of the National Academy of Sciences USA 80: 3734–3737.
Fenteany, G., P.A. Janmey and T.P. Stossel (2000). Signaling pathways and cell mechanics involved in wound closure by epithelial cell sheets. Current Biology 10: 831–838.
Funasaka, T., A. Haga, A. Raz and H. Nagase (2001). Tumor autocrine motility factor is an angiogenic factor that stimulates endothelial cell motility. Biochemical and Biophysical Research Communications 285: 118–128.
Galiacy, S., E. Planus, H. Lepetit, S. Fereol, V. Laurent, L. Ware, D. Isabey, M. Matthay, A. Harf and M.P. d'Ortho (2003). Keratinocyte growth factor promotes cell motility during alveolar epithelial repair in vitro. Experimental Cell Research 283: 215–229.
Ingber, D.E. (2002). Mechanical signaling and the cellular response to extracellular matrix in angiogenesis and cardiovascular physiology. Circulation Research 91: 877–887.
Kiernan, B. W. and C. Ffrench-Constant (1993). Oligodendrocyte precursor (0-2A progenitor cell) migration; a model system for the study of cell migration in the developing central nervous system. Development, Supplement: 219–225.
Klepeis, V.E., A. Cornell-Bell and V. Trinkaus-Randall (2001). Growth factors but not gap junctions play a role in injury-induced ca2+ waves in epithelial cells. Journal of Cell Science 114: 4185–95.
Kouvroukoglou, S., KC. Dee, R. Bizios, L.V. McIntire and K. Zygourakis (2000). Endothelial cell migration on surfaces modified with immobilized adhesive peptides. Biomaterials 21: 1725–1733
Lauffenburger, D.A.L.G. and Griffith (2001). Who's got pull around here? Cell organization in development and tissue engineering. Proceedings of the National Academy of Sciences USA 98: 4282–4284.
Maheshwari, G. and D.A. Lauffenburger (1998) Deconstructing (and reconstructing) cell migration. Microscopy Research Technology 43: 358–368.
Manes, S., E. Mira, C. Gomez-Mouton, R.A. Lacalle and C. Martinez (2000). Cells on the move: a dialogue between polarization and motility. IUBMB Life 4939–96.
Mansury, Y. and T.S. Deisboeck (2003). The impact of "search precision" in an agent-based tumor model. Journal of Theoretical Biology 224: 325–337.
Palecek, S.P., J.C. Loftus, M.H. Ginsberg, D.A. Lauffenburger and A.F. Horwitz (1997). Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness. Nature 385: 537–540.
Planus, E., S. Galiacy, M. Matthay, V. Laurent, J. Gavrilovic, G. Murphy, C. Clerici, D. Isabey, C. Lafuma and M.P. d'Ortho (1999). Role of collagenase in mediating in vitro alveolar epithelial wound repair. Journal of Cell Science 112: 243–252.
Promayon, E., J.L. Martiel and P. Tracqui (2003). Physical-object-oriented 3D simulations of cell deformations and migration. In: Alt, W., M. Chaplain, M. Griebel and J. Lenz (Eds). Polymer and cell dynamics-Multiscale modeling and numerical simulations. pp. 125–138. Birkhäuser, Basel.
Ronot, X., A. Doisy and P. Tracqui (2000). Quantitative study of dynamic behavior of cell monolayers during in vitro wound healing by optical flow analysis. Cytometry 41: 19–30.
Salva, U., L.E. Olson and C.M. Waters (2004). Mathematical modeling of airway epithelial wound closure during cyclic mechanical strain. Journal of Applied Physiology 96: 566–574.
Shvartsman, S.Y., H.S. Wiley, W.M. Deen and D.A. Lauffenburger (2001). Spatial range of autocrine signaling: modeling and computational analysis. Biophysical Journal 81: 1854–1867.
Soll, DR. and E. Voss (1999). Two-and three-dimensional computer systems for analyzing how animal cells crawl. In: Soll, D. R. and D. Wessels (Eds) Motion analysis of living cells. pp. 26–52. Wiley-Liss, London.
Tan, J., H. Shen and W.M. Saltzman (2001). Micron-scale positioning of features influences the rate of polymorphonuclear leukocyte migration. Biophysical Journal 81: 2569–2579.
Tranqui, L. and P. Tracqui (2000). Mechanical signaling and angiogenesis: the integration of cell-extracellular matrix couplings, Comptes Rendus de 1'Académie des Sciences, Série 111 322: 1–17.
Vailhé, B., X. Ronot, P. Tracqui, Y. Usson and L. Tranqui (1997). In vitro angiogenesis is modulated by the mechanical properties of fibrin gels and is related to βv β3 integrin localization. In Vitro Cellular and Developmental Biology Animal, 33: 763–773.
Varani, J. and PA. Ward (1978). A comparison of the migration patterns of normal and malignant cells in two assays systems. American Journal of Pathology 90: 159–172.
Vernon, R.B. and M.D. Gooden (2002). New technologies in vitro for analysis of cell movement on or within collagen gels, Matrix Biology 21: 661–669.
Zahm, JM., H. Kaplan, A.L. Herard, F. Doriot, D. Pierrot, P. Somelette and E. Puchelle (1997). Cell migration and proliferation during the in vitro wound repair of the respiratory epithelium. Cell Motility and the Cytoskeleton 37: 3343
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Rosello, C., Ballet, P., Planus, E. et al. Model Driven Quantification of Individual and Collective Cell Migration. Acta Biotheor 52, 343–363 (2004). https://doi.org/10.1023/B:ACBI.0000046602.58202.5e
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DOI: https://doi.org/10.1023/B:ACBI.0000046602.58202.5e