Actin Filaments as Tension Sensors

Galkin, Vitold E.; Orlova, Albina; Egelman, Edward H.

doi:10.1016/j.cub.2011.12.010

Cited by 158 publications

(145 citation statements)

References 50 publications

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“…1B). A previous observation using the compression of actin filaments between two thin mica plates observed a stiffening of these filaments under force (Greene et al, 2009), which appears to be the same phenomenon as the rigidification of F-actin observed in thin ice (Galkin et al, 2012). In order to reduce structural heterogeneity within the actin filament to achieve the highest possible resolution we used blotting conditions (see Materials and Methods) which yielded very thin ice (Fig.…”

Section: Resultssupporting

confidence: 59%

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Near-Atomic Resolution for One State of F-Actin

Galkin

Orlova

Vos³

et al. 2015

Structure

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Actin functions as a helical polymer, F-actin, but attempts to build an atomic model for this filament have been hampered by the fact that the filament cannot be crystallized and by structural heterogeneity. We have used a direct electron detector, electron cryo-microscopy and the forces imposed on actin filaments in thin films to reconstruct one state of the filament at 4.7 Å resolution, which allows for building the first reliable pseudo-atomic model of F-actin. We also report a different state of the filament where actin protomers adopt a conformation observed in the crystal structure of the G-actin-profilin complex with an open ATP-binding cleft. Comparison of the two structural states provides new insights into ATP-hydrolysis and filament dynamics. The atomic model provides a framework for understanding why every buried residue in actin has been under intense selective pressure.

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Section: Resultssupporting

confidence: 59%

“…We recently suggested that the structural state of actin filaments can be modulated by applied forces (Galkin et al, 2012). Samples are prepared for cryo-EM by blotting a drop applied to a grid so that only a thin film remains, which is then rapidly frozen.…”

Section: Resultsmentioning

confidence: 99%

Near-Atomic Resolution for One State of F-Actin

Galkin

Orlova

Vos³

et al. 2015

Structure

Self Cite

135

154

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“…The link between the mechanics of actin filaments, ADF/cofilin, and severing was further investigated using optical tweezers to stretch actin filaments, revealing that stretched actin filaments are resistant to ADF/cofilin binding/severing (95,117). This observation is in line with the idea that actin filaments may act as tension sensors to modulate their own dynamics.…”

Section: Adf/cofilin-induced Disassemblysupporting

confidence: 64%

Actin Dynamics, Architecture, and Mechanics in Cell Motility

Blanchoin

Boujemaa-Paterski

Sykes

et al. 2014

Physiological Reviews

1,242

1,145

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Tight coupling between biochemical and mechanical properties of the actin cytoskeleton drives a large range of cellular processes including polarity establishment, morphogenesis, and motility. This is possible because actin filaments are semi-flexible polymers that, in conjunction with the molecular motor myosin, can act as biological active springs or "dashpots" (in laymen's terms, shock absorbers or fluidizers) able to exert or resist against force in a cellular environment. To modulate their mechanical properties, actin filaments can organize into a variety of architectures generating a diversity of cellular organizations including branched or crosslinked networks in the lamellipodium, parallel bundles in filopodia, and antiparallel structures in contractile fibers. In this review we describe the feedback loop between biochemical and mechanical properties of actin organization at the molecular level in vitro, then we integrate this knowledge into our current understanding of cellular actin organization and its physiological roles. I. PREFACE ON ACTIN ORGANIZATION AND CELL MECHANICSAnimal cells (i.e., those without a cell wall) have the ability to change their shape to adapt to their environment, move through narrow spaces, divide, or allow exo-and endocytosis. The machinery of these shape changes relies on the assembly of proteins, in particular actin, a globular protein that polymerizes into filaments of different types of organization: branched and crosslinked networks, parallel bundles, and anti-parallel contractile structures (FIGURE 1A). These different architectures can be envisioned as a series of interconnected active springs and dashpots (green and red symbols in FIGURE 1B, respectively) that act as mechanical elements to drive cell shape changes and motility. The purpose of this review is to correlate recent progress in our understanding of the interplay between biochemical elements and mechanical properties. Instead of describing biochemical and mechanical properties separately, our main goal here is to address piece by piece the integrated feedback loop between biochemistry and mechanics.At the front of the cell, branched and crosslinked networks in a quasi two-dimensional sheet make up the lamellipodium, and are the major engine of cell movement since they push the cell membrane by polymerizing against it (FIGURE 1A, iii). Aligned bundles underlie filopodia that are the fingerlike structures at the front of the cell, important for directional response of the cell (FIGURE 1A, iv). A thin layer of actin, called the cell cortex, coats the plasma membrane at the back and sides of the cell, important for cell shape maintenance and changes (FIGURE 1A, i). The rest of the cell contains a three-dimensional network of crosslinked filaments interspersed with contractile bundles, including stress fibers that connect the cell cytoskeleton to the extracellular matrix via focal adhesion sites (FIGURE 1A, ii). Contraction in the cell is produced by the molecular motor protein myosin. Myosin assembles into anti...

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“…Our understanding of actin SFs has evolved from a static cable of actin to a flexible, dynamic structure that functions as a tension sensor [27]. Actin SFs anchor at sites of integrin-based FAs forming a complex interface between SFs and FAs.…”

Section: Regulation Of Force By Stress Fibersmentioning

confidence: 99%

LIM proteins in actin cytoskeleton mechanoresponse

Smith

Hoffman

Beckerle

2014

Trends in Cell Biology

111

112

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The actin cytoskeleton assembles into branched networks or bundles to generate mechanical force for critical cellular processes such as establishment of polarity, adhesion, and migration. Stress fibers are contractile, actomyosin structures that physically couple to the extracellular matrix through integrin-based focal adhesions, thereby transmitting force into and across the cell. Recently, LIM domain proteins have been implicated in mediating this cytoskeletal mechanotransduction. Among the more well studied LIM domain adapter proteins is zyxin, a dynamic component of both focal adhesions and stress fibers. Here, we discuss recent research detailing the mechanisms by which stress fibers adjust their structure and composition to balance mechanical forces, and suggest ways zyxin and other LIM domain proteins mediate mechanoresponse.

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Actin Filaments as Tension Sensors

Cited by 158 publications

References 50 publications

Near-Atomic Resolution for One State of F-Actin

Near-Atomic Resolution for One State of F-Actin

Actin Dynamics, Architecture, and Mechanics in Cell Motility

LIM proteins in actin cytoskeleton mechanoresponse

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