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

Molecular Biology of the Cell
Setareh DolatiMartin Falcke

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 ...Continue Reading

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Citations

Feb 26, 2020·Journal of Cell Science·Georgi DimchevKlemens Rottner
Jul 11, 2020·Science Immunology·Elisabeth SalzerKaan Boztug
Jan 24, 2021·Proceedings of the National Academy of Sciences of the United States of America·Christoph SchreiberMartin Falcke
Jan 12, 2020·Experimental Cell Research·Xiaoying GuanZuoyi Jiao

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Methods Mentioned

BETA
confocal microscopy
transfections
transfection
PCRs

Software Mentioned

Visiview
ImageJ
Elements
Andromeda
NIS
MetaMorph
MaxQuant

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