On the relation between filament density, force generation, and protrusion rate in mesenchymal cell motility

S. Dolati, F. Kage, J. Mueller, M. Müsken, M. Kirchner, G. Dittmar, M.K. Sixt, K. Rottner, M. Falcke, Molecular Biology of the Cell 29 (2018) 2674–2686.

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Abstract
Lamellipodia are flat membrane protrusions formed during mesenchymal motion. Polymerization at the leading edge assembles the actin filament network and generates protrusion force. How this force is supported by the network and how the assembly rate is shared between protrusion and network retrograde flow determines the protrusion rate. We use mathematical modeling to understand experiments changing the F-actin density in lamellipodia of B16-F1 melanoma cells by modulation of Arp2/3 complex activity or knockout of the formins FMNL2 and FMNL3. Cells respond to a reduction of density with a decrease of protrusion velocity, an increase in the ratio of force to filament number, but constant network assembly rate. The relation between protrusion force and tension gradient in the F-actin network and the density dependency of friction, elasticity, and viscosity of the network explain the experimental observations. The formins act as filament nucleators and elongators with differential rates. Modulation of their activity suggests an effect on network assembly rate. Contrary to these expectations, the effect of changes in elongator composition is much weaker than the consequences of the density change. We conclude that the force acting on the leading edge membrane is the force required to drive F-actin network retrograde flow.
Publishing Year
Date Published
2018-11-01
Journal Title
Molecular Biology of the Cell
Volume
29
Issue
22
Page
2674-2686
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Dolati S, Kage F, Mueller J, et al. On the relation between filament density, force generation, and protrusion rate in mesenchymal cell motility. Molecular Biology of the Cell. 2018;29(22):2674-2686. doi:10.1091/mbc.e18-02-0082
Dolati, S., Kage, F., Mueller, J., Müsken, M., Kirchner, M., Dittmar, G., … Falcke, M. (2018). On the relation between filament density, force generation, and protrusion rate in mesenchymal cell motility. Molecular Biology of the Cell, 29(22), 2674–2686. https://doi.org/10.1091/mbc.e18-02-0082
Dolati, Setareh, Frieda Kage, Jan Mueller, Mathias Müsken, Marieluise Kirchner, Gunnar Dittmar, Michael K Sixt, Klemens Rottner, and Martin Falcke. “On the Relation between Filament Density, Force Generation, and Protrusion Rate in Mesenchymal Cell Motility.” Molecular Biology of the Cell 29, no. 22 (2018): 2674–86. https://doi.org/10.1091/mbc.e18-02-0082.
S. Dolati et al., “On the relation between filament density, force generation, and protrusion rate in mesenchymal cell motility,” Molecular Biology of the Cell, vol. 29, no. 22, pp. 2674–2686, 2018.
Dolati S, Kage F, Mueller J, Müsken M, Kirchner M, Dittmar G, Sixt MK, Rottner K, Falcke M. 2018. On the relation between filament density, force generation, and protrusion rate in mesenchymal cell motility. Molecular Biology of the Cell. 29(22), 2674–2686.
Dolati, Setareh, et al. “On the Relation between Filament Density, Force Generation, and Protrusion Rate in Mesenchymal Cell Motility.” Molecular Biology of the Cell, vol. 29, no. 22, American Society for Cell Biology , 2018, pp. 2674–86, doi:10.1091/mbc.e18-02-0082.
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