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

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Item Type:Article
Title:On the relation between filament density, force generation and protrusion rate in mesenchymal cell motility
Creators Name:Dolati, S. and Kage, F. and Mueller, J. and Müsken, M. and Kirchner, M. and Dittmar, G. and Sixt, M. and Rottner, K. and Falcke, M.
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 modelling 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.
Keywords:Cell Motility, B16-F1 Melanoma, Formin, Arp2/3 Complex, Cellular Biophysics, Mathematical Modelling
Source:Molecular Biology of the Cell
ISSN:1059-1524
Publisher:American Society for Cell Biology (U.S.A.)
Volume:29
Number:22
Page Range:2674-2686
Date:1 November 2018
Official Publication:https://doi.org/10.1091/mbc.E18-02-0082
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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