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How actin crosslinking and bundling proteins cooperate to generate an enhanced cell mechanical responseActin-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, alpha-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 alpha-actinin and fascin elicits a cell mechanical response that is significantly greater than that originated by alpha-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 alpha-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 alpha-actinin and fascin. These findings highlight the cooperative activity of fascin and alpha-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.
Document ID
20050218654
Acquisition Source
Johnson Space Center
Document Type
Reprint (Version printed in journal)
Authors
Tseng, Yiider
(The Johns Hopkins University Baltimore, MD 21218, United States)
Kole, Thomas P.
Lee, Jerry S H.
Fedorov, Elena
Almo, Steven C.
Schafer, Benjamin W.
Wirtz, Denis
Date Acquired
August 23, 2013
Publication Date
August 19, 2005
Publication Information
Publication: Biochemical and biophysical research communications
Volume: 334
Issue: 1
ISSN: 0006-291X
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: NAG9-1563
CONTRACT_GRANT: GM 075305
CONTRACT_GRANT: AR 42047
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Discipline Cell Biotechnology

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