How actin crosslinking and bundling proteins cooperate to generate an enhanced cell mechanical response

Yiider Tseng, Thomas P. Kole, Jerry S.H. Lee, Elena Fedorov, Steven C. Almo, Benjamin W. Schafer, Denis Wirtz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

100 Scopus citations


Actin-crosslinking proteins organize actin filaments into dynamic and complex subcellular scaffolds that orchestrate important mechanical functions, including cell motility and adhesion. Recent mutation studies have shown that individual crosslinking proteins often play seemingly non-essential roles, leading to the hypothesis that they have considerable redundancy in function. We report live-cell, in vitro, and theoretical studies testing the mechanical role of the two ubiquitous actin-crosslinking proteins, α-actinin and fascin, which co-localize to stress fibers and the basis of filopodia. Using live-cell particle tracking microrheology, we show that the addition of α-actinin and fascin elicits a cell mechanical response that is significantly greater than that originated by α-actinin or fascin alone. These live-cell measurements are supported by quantitative rheological measurements with reconstituted actin filament networks containing pure proteins that show that α-actinin and fascin can work in concert to generate enhanced cell stiffness. Computational simulations using finite element modeling qualitatively reproduce and explain the functional synergy of α-actinin and fascin. These findings highlight the cooperative activity of fascin and α-actinin and provide a strong rationale that an evolutionary advantage might be conferred by the cooperative action of multiple actin-crosslinking proteins with overlapping but non-identical biochemical properties. Thus the combination of structural proteins with similar function can provide the cell with unique properties that are required for biologically optimal responses.

Original languageEnglish
Pages (from-to)183-192
Number of pages10
JournalBiochemical and Biophysical Research Communications
Issue number1
StatePublished - 19 Aug 2005
Externally publishedYes


  • Actin
  • Cell mechanics
  • Cytoskeleton
  • Fascin
  • Multiple-particle tracking microrheology
  • α-Actinin


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