Literature Review

Literature review: Mechanism of cell migration and cell sensing

Congyingzi Zhang

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Cell migration is a common but important cell behavior relating to development, diseases, and maintaining the stability in multicellular organisms. Cell migration has been demonstrated driving many development stages in embryogenesis by cell specification, hindgut expansion, gastrulation, early gonad formation, and some other embryonic development processes. Besides being helpful to understand the early embryogenesis, another reason that cell migration has been studied is its therapeutic role in cancer biology and related drug designing. Tissue invasion is a crucial step in the tumor metastasis and has been demonstrated closely related to cell migration by actin dynamics. In tumor cells, bundled or densely arrayed actins filament form filopodia and lamellipodia on the cell leading edge during migration helping the invasion process with the presence of matrix degradation (Vignjevic & Montagnac, 2008). Additionally, neurogenesis and neuron development are closely linked with cell migration. Neuron cells have to elongate from their birth site with the facilitation of cytoskeleton construction. Failure in migration might lead to severe neuron development disorder related diseases (Gleeson & Walsh, 2000). In any multicellular organism, the sustenance of system stability is undoubtedly important; wound healing is one example. Once a wound is created on an epithelial cells covered surface, the cells will have the potential to close the gap through cell migration and cell proliferation, which is meaningful to the maintenance of any living system, cell migration research, and biomaterial application in tissue engineering (Tremel et al., 2009).

The migration process is initialed by the polarization, which could be induced by applying microscopic nonuniformities or changing the receptor-ligand binding kinetics. Polarization determines that the cell has its front and rear regions during the migration process, which is earmarked by the membrane protruding structures activities. There are two kinds of membrane protruding structures which could be found near the cell front edge. One is the needle-like filopodia, regulated by cdc42, and the other is the sheet-like lamellipodia regulated by rac. The formation of these two kinds of protrusions is the consequence of local actin polymerization and crosslink which provides the protrusive force for the migration process. The other cell translocation force helping the migration process is the contractile force, which is believed to be related to the myosin-actin interaction. A third membrane structure playing a key role in providing translocation force is the focal adhesions. Small new focal adhesions regulated by rho, which is initialed by the activation of cdc42 form behind the lamellipodia and fix to the substrate. It is believed that the formation of the adhesive complex is comprised by phosphoprotein covalently modified by tyrosine phosphorylation.  The detachment of the focal adhesions near the rear edge will disrupt the cell-substrate conjunctions, which release the cell from the reaction of the substrate.

Cell migration could be quantified by two indexes, linear cell locomotion speed and directional persistence time, which are the description or the measurement of the migration speed and its consistency of migrating direction. Usually, the linear cell locomotion speed inversely correlates with the contractile force. The coordination between the directional signal and the physical movement leads to the inverse correlation between the migration speed and the persistence of the moving direction. Because the membrane protrudes near the cell front, the cell then changes its walking direction randomly, which is named random walking (Lauffenburger & Horwitz, 1996).

Though cells could wander randomly on the substrate when certain inducements are applied, the two indexes mentioned above could be controlled on some extent for specific studies. A series of research demonstrate the linear cell locomotion speed could be manipulated by using various growth factors. Platelet-derived growth factor (PDGF-BB) has been found to promote the bone tissue injury in vivo and to have significant healing effect in the ‘scratch’ assay in vitro (Chung et al., 2009). More research showed the insulin-like growth factors could stimulate the tissue invasion and tumor metastasis by promoting cell migration (Guvakova, 2007). In lung cancer research, it was suggested that the interaction between the ion channel TRPM7 and the epidermal growth factor (EGF) was required for tumor development related cell migration (Gao et al., 2011). The directional persistence could be related to the cell sensory mechanism. It has been demonstrated that the filopodia has been used by cells to sense the external environment (Mellor, 2010). Furthermore, evidence showed the small adhesions formed in the filopodia focal complex (filopodial FX) right behind along the filopodia axis. When lamellipodia substitute those regions, those small adhesions get matured into classic focal adhesions. The filopodia then could elongate again for further migration. This evidence suggested that the filopodia are responsible for the sensory mechanism in the cell migration (Schäfer et al., 2009). More evidence on the molecular level is needed for further explanation of the correlation between the filopodia formation and the protein composition depends on the co-culturing medium and gradient substrate.

REFERENCE

Vignjevic, D., Montagnac, G., 2008. Reorganisation of the dendritic actin network during cancer cell migration and invasion. Seminars in Cancer Biology 18, 12-22.

Gleeson, J., Walsh, C., 2000. Neuronal migration disorders: from genetic diseases to developmental mechanisms. Trends in Neurosciences 23, 352-359.

Tremel, A., Cai, A., Tirtaatmadja, N., Hughes, B.D., Stevens, G.W., Landman, K.A., O’Connor, A.J., 2009. Cell migration and proliferation during monolayer formation and wound healing. Chemical Engineering Science 64, 247-253.

Lauffenburger D.A., Horwitz A.F.,1996. Cell migration: A physically integrated molecular process. Cell 84,359-369.

Chung, R., Foster, B.K., Zannettino, A.C.W., Xian, C.J., 2009. Potential roles of growth factor PDGF-BB in the bony repair of injured growth plate. Bone 44, 878-885.

Guvakova, M.A., 2007. Insulin-like growth factors control cell migration in health and disease. The International Journal of Biochemistry & Cell Biology 39, 890-909.

Gao, H., Chen, X., Du, X., Guan, B., Liu, Y., Zhang, H., 2011. EGF enhances the migration of cancer cells by up-regulation of TRPM7. Cell Calcium 50, 559-568.

Mellor, H., 2010. The role of formins in filopodia formation. Biochimica et Biophysica Acta (BBA) – Molecular Cell Research 1803, 191-200.

Schäfer, C., Borm, B., Born, S., Möhl, C., E.M., Hoffmann, B., 2009. One step ahead: Role of filopodia in adhesion formation during cell migration of keratinocytes. Experimental Cell Research 315, 1212-1224.