Membrane-proximal F-actin restricts local membrane protrusions and directs cell migration
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Updated: Dec 18, 2025
Measuring Cell-Edge Protrusion Dynamics during Spreading using Live-Cell Microscopy
Published on: November 1, 2021
Anjali Bisaria1, Arnold Hayer2, Damien Garbett2
1Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA, USA. abisaria@stanford.edu tom4003@med.cornell.edu.
Abstract:
Cell migration is driven by local membrane protrusion through directed polymerization of F-actin at the front. However, F-actin next to the plasma membrane also tethers the membrane and thus resists outgoing protrusions. Here, we developed a fluorescent reporter to monitor changes in the density of membrane-proximal F-actin (MPA) during membrane protrusion and cell migration. Unlike the total F-actin concentration, which was high in the front of migrating cells, MPA density was low in the front and high in the back. Back-to-front MPA density gradients were controlled by higher cofilin-mediated turnover of F-actin in the front. Furthermore, nascent membrane protrusions selectively extended outward from areas where MPA density was reduced. Thus, locally low MPA density directs local membrane protrusions and stabilizes cell polarization during cell migration.
Insights
Membrane-proximal actin (MPA) density, not total actin, directs cell protrusion. Low MPA at the cell front drives membrane extension, stabilizing cell migration and polarization.
Area of Science:
- Cell Biology
- Biophysics
- Molecular Motors
Background:
- Cell migration relies on actin polymerization for membrane protrusion.
- Membrane-proximal actin (MPA) can impede protrusion by tethering the cell membrane.
Purpose of the Study:
- To develop a method for visualizing and quantifying MPA dynamics during cell migration.
- To investigate the role of MPA density gradients in directing membrane protrusions and cell polarization.
Main Methods:
- Development of a novel fluorescent reporter for membrane-proximal F-actin (MPA).
- Live-cell imaging to monitor MPA density changes during cell migration.
- Analysis of F-actin turnover rates and their correlation with MPA distribution.
Main Results:
- MPA density was found to be low at the leading edge and high at the rear of migrating cells.
- A back-to-front gradient in MPA density was established by increased F-actin turnover at the front, regulated by cofilin.
- New membrane protrusions initiated specifically from regions with reduced MPA density.
Conclusions:
- Locally decreased MPA density is a key regulator of directed membrane protrusion during cell migration.
- MPA density gradients play a critical role in stabilizing cell polarity and directing migration.
- This study reveals a novel mechanism controlling cell movement at the molecular level.
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