Cell elasticity is regulated by the tropomyosin isoform composition of the actin cytoskeleton

Iman Jalilian, Celine Heu, Hong Cheng, Hannah Freittag, Melissa Desouza, Justine R. Stehn, Nicole S. Bryce, Renee M. Whan, Edna C. Hardeman, Thomas Fath, Galina Schevzov, Peter W. Gunning

Research output: Contribution to journalArticle

28 Citations (Scopus)
2 Downloads (Pure)

Abstract

The actin cytoskeleton is the primary polymer system within cells responsible for regulating cellular stiffness. While various actin binding proteins regulate the organization and dynamics of the actin cytoskeleton, the proteins responsible for regulating the mechanical properties of cells are still not fully understood. In the present study, we have addressed the significance of the actin associated protein, tropomyosin (Tpm), in influencing the mechanical properties of cells. Tpms belong to a multi-gene family that form a co-polymer with actin filaments and differentially regulate actin filament stability, function and organization. Tpm isoform expression is highly regulated and together with the ability to sort to specific intracellular sites, result in the generation of distinct Tpm isoform-containing actin filament populations. Nanomechanical measurements conducted with an Atomic Force Microscope using indentation in Peak Force Tapping in indentation/ramping mode, demonstrated that Tpm impacts on cell stiffness and the observed effect occurred in a Tpm isoform-specific manner. Quantitative analysis of the cellular filamentous actin (F-actin) pool conducted both biochemically and with the use of a linear detection algorithm to evaluate actin structures revealed that an altered F-actin pool does not absolutely predict changes in cell stiffness. Inhibition of non-muscle myosin II revealed that intracellular tension generated by myosin II is required for the observed increase in cell stiffness. Lastly, we show that the observed increase in cell stiffness is partially recapitulated in vivo as detected in epididymal fat pads isolated from a Tpm3.1 transgenic mouse line. Together these data are consistent with a role for Tpm in regulating cell stiffness via the generation of specific populations of Tpm isoformcontaining actin filaments.

Original languageEnglish
Article numbere0126214
Pages (from-to)1-23
Number of pages23
JournalPLoS ONE
Volume10
Issue number5
DOIs
Publication statusPublished - 15 May 2015
Externally publishedYes

Bibliographical note

Copyright the Author(s) 2015. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Fingerprint Dive into the research topics of 'Cell elasticity is regulated by the tropomyosin isoform composition of the actin cytoskeleton'. Together they form a unique fingerprint.

  • Cite this

    Jalilian, I., Heu, C., Cheng, H., Freittag, H., Desouza, M., Stehn, J. R., ... Gunning, P. W. (2015). Cell elasticity is regulated by the tropomyosin isoform composition of the actin cytoskeleton. PLoS ONE, 10(5), 1-23. [e0126214]. https://doi.org/10.1371/journal.pone.0126214