Vimentin intermediate filaments and filamentous actin form unexpected interpenetrating networks that redefine the cell cortex

Huayin Wu, Yinan Shen, Suganya Sivagurunathan, Miriam Sarah Weber, Stephen A. Adam, Jennifer H. Shin, Jeffrey J. Fredberg, Ohad Medalia, Robert Goldman, David A. Weitz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


The cytoskeleton of eukaryotic cells is primarily composed of networks of filamentous proteins, F-actin, microtubules, and intermediate filaments. Interactions among the cytoskeletal components are important in determining cell structure and in regulating cell functions. For example, F-actin and microtubules work together to control cell shape and polarity, while the subcellular organization and transport of vimentin intermediate filament (VIF) networks depend on their interactions with microtubules. However, it is generally thought that F-actin and VIFs form two coexisting but separate networks that are independent due to observed differences in their spatial distribution and functions. In this paper, we present a closer investigation of both the structural and functional interplay between the F-actin and VIF cytoskeletal networks. We characterize the structure of VIFs and F-actin networks within the cell cortex using structured illumination microscopy and cryoelectron tomography. We find that VIFs and F-actin form an interpenetrating network (IPN) with interactions at multiple length scales, and VIFs are integral components of F-actin stress fibers. From measurements of recovery of cell contractility after transient stretching, we find that the IPN structure results in enhanced contractile forces and contributes to cell resilience. Studies of reconstituted networks and dynamic measurements in cells suggest direct and specific associations between VIFs and F-actin. From these results, we conclude that VIFs and F-actin work synergistically, both in their structure and in their function. These results profoundly alter our understanding of the contributions of the components of the cytoskeleton, particularly the interactions between intermediate filaments and F-actin.

Original languageEnglish (US)
Article numbere2115217119
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number10
StatePublished - Mar 8 2022


  • Cell cortex
  • High-resolution imaging
  • Interpenetrating networks of F-actin and vimentin intermediate filaments
  • Traction force microscopy

ASJC Scopus subject areas

  • General


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