Actin cap associated focal adhesions and their distinct role in cellular mechanosensing

Dong Hwee Kim, Shyam B. Khatau, Yunfeng Feng, Sam Walcott, Sean X. Sun, Gregory D. Longmore, Denis Wirtz

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144 Citations (Scopus)


The ability for cells to sense and adapt to different physical microenvironments plays a critical role in development, immune responses, and cancer metastasis. Here we identify a small subset of focal adhesions that terminate fibers in the actin cap, a highly ordered filamentous actin structure that is anchored to the top of the nucleus by the LINC complexes; these differ from conventional focal adhesions in morphology, subcellular organization, movements, turnover dynamics, and response to biochemical stimuli. Actin cap associated focal adhesions (ACAFAs) dominate cell mechanosensing over a wide range of matrix stiffness, an ACAFA-specific function regulated by actomyosin contractility in the actin cap, while conventional focal adhesions are restrictively involved in mechanosensing for extremely soft substrates. These results establish the perinuclear actin cap and associated ACAFAs as major mediators of cellular mechanosensing and a critical element of the physical pathway that transduce mechanical cues all the way to the nucleus.

Original languageEnglish
Article number555
JournalScientific reports
Publication statusPublished - 2012
Externally publishedYes

Bibliographical note

Funding Information:
The authors thank Dr. Didier Hodzic (Washington University in St. Louis, School of Medicine) for providing us with KASH constructs and Dr. Pekka Lappalainen (University of Helsinki, Finland) for helpful discussions about the fundamental differences between dorsal actin fibers/arcs and actin cap fibers discussed in this paper. This work was supported by NIH grants R01GM084204 and U54CA143868.

ASJC Scopus subject areas

  • General


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