Assembly kinetics determine the architecture of α-actinin crosslinked F-actin networks

Falzone, Tobias T.; Lenz, Martin; Kovar, David R.; Gardel, Margaret L.

doi:10.1038/ncomms1862

Cited by 92 publications

(119 citation statements)

References 36 publications

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“…Unlike the Arp2/3 complex, which is involved both in the initiation of actin assembly and in the organization of the network, crosslinking proteins play no or little role during actin assembly, but connect already polymerized actin filaments together to generate a complex macroscopic organization (FIGURE 3, B-D, and Refs. 85,129,148,331). An identifying property of each crosslinking protein is the distance by which it bridges two actin filaments (FIGURE 3, B AND C); crosslink distances range from 10 nm for fimbrin to 160 nm for filamin (153,282,297).…”

Section: Crosslinked Actin Networkmentioning

confidence: 99%

“…Larger crosslinkers, such as filamin or ␣-actinin, are present in either bundles or networks depending on their concentrations (69,148,199,277,329,330). In addition, recent results show that the rate of assembly of actin networks can influence how crosslinkers do their job through crowding effects (85). Indeed, increasing the rate of actin assembly abolishes the formation of actin bundles generated by ␣-actinin because fast actin assembly generates long filaments that have limited mobility, preventing them from being aligned into bundles by this crosslinker (85).…”

Section: Crosslinked Actin Networkmentioning

confidence: 99%

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Actin Dynamics, Architecture, and Mechanics in Cell Motility

Blanchoin

Boujemaa-Paterski

Sykes

et al. 2014

Physiological Reviews

1,237

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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Section: Crosslinked Actin Networkmentioning

confidence: 99%

Section: Crosslinked Actin Networkmentioning

confidence: 99%

Actin Dynamics, Architecture, and Mechanics in Cell Motility

Blanchoin

Boujemaa-Paterski

Sykes

et al. 2014

Physiological Reviews

1,237

1,145

View full text Add to dashboard Cite

show abstract

“…The architecture of cross-linked actin networks is determined both by filament assembly dynamics (rate of nucleation, growth, and severing) and by factors controlling cross-linking (cross-link kinetics and concentration) and actin filament concentration and length (66,67). In the absence of cross-linkers, assembled filaments display a homogeneous distribution with a relatively uniform average distance between filaments (termed the "mesh size").…”

Section: Control Over Actin Network and Bundle Architecturementioning

confidence: 99%

“…Steric entanglements constrain filament motions and, consequently, give rise to viscoelastic behavior (68,69). Steric entanglements also prevent realignment of filaments into bundles (66). Thus, the architecture of cross-linked networks is determined by competing timescales of bundle formation and the arrested mobility that occurs with entanglement.…”

Section: Control Over Actin Network and Bundle Architecturementioning

confidence: 99%

“…For a given cross-link type and density, fast growing filaments form fine meshworks, whereas slowly elongating filaments form networks of dense bundles (70). Thus, architecture of cross-linked actin network is kinetically determined, reflecting an arrested or kinetically "trapped" state rather than the lowest energy state defined by true thermodynamic equilibrium (66,71).…”

Section: Control Over Actin Network and Bundle Architecturementioning

confidence: 99%

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Actin Mechanics and Fragmentation

Cruz

Gardel

2015

Journal of Biological Chemistry

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Cell physiological processes require the regulation and coordination of both mechanical and dynamical properties of the actin cytoskeleton. Here we review recent advances in understanding the mechanical properties and stability of actin filaments and how these properties are manifested at larger (network) length scales. We discuss how forces can influence local biochemical interactions, resulting in the formation of mechanically sensitive dynamic steady states. Understanding the regulation of such force-activated chemistries and dynamic steady states reflects an important challenge for future work that will provide valuable insights as to how the actin cytoskeleton engenders mechanoresponsiveness of living cells.

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Crowding tunes the organization and mechanics of actin bundles formed by crosslinking proteins

Park

Lee

et al. 2020

FEBS Letters

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Fascin and α‐actinin form higher‐ordered actin bundles that mediate numerous cellular processes including cell morphogenesis and movement. While it is understood crosslinked bundle formation occurs in crowded cytoplasm, how crowding affects the bundling activities of the two crosslinking proteins is not known. Here, we demonstrate how solution crowding modulates the organization and mechanical properties of fascin‐ and α‐actinin‐induced bundles, utilizing total internal reflection fluorescence and atomic force microscopy imaging. Molecular dynamics simulations support the inference that crowding reduces binding interaction between actin filaments and fascin or the calponin homology 1 domain of α‐actinin evidenced by interaction energy and hydrogen bonding analysis. Based on our findings, we suggest a mechanism of crosslinked actin bundle assembly and mechanics in crowded intracellular environments.

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Assembly kinetics determine the architecture of α-actinin crosslinked F-actin networks

Cited by 92 publications

References 36 publications

Actin Dynamics, Architecture, and Mechanics in Cell Motility

Actin Dynamics, Architecture, and Mechanics in Cell Motility

Actin Mechanics and Fragmentation

Crowding tunes the organization and mechanics of actin bundles formed by crosslinking proteins

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