Mechanical unfolding of single filamin A (ABP‐280) molecules detected by atomic force microscopy

Furuike, Shou; Ito, Tomoaki; Yamazaki, Masahito

doi:10.1016/s0014-5793(01)02497-8

Cited by 119 publications

(126 citation statements)

References 24 publications

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“…The mechanical response of the composite FLNa-F-actin networks eludes either the current theoretical models for entangled F-actin solutions or those for rigidly cross-linked F-actin networks. Instead, we speculate that the FLNa cross-links mediate the dynamic nonlinear mechanical response of these networks through an interplay between the nonlinear divergence of the stiffness of individual semiflexible FLNa cross-links with a force-and time-dependent unfolding of sheets within the FLNa molecule [15] as well as binding kinetics of the FLNa molecule with F-actin. Alternatively, current models of prestressed structures suggest that their mechanical response depends very weakly on the elasticity of the individual elements [23].…”

Section: Prl 96 088102 (2006) P H Y S I C a L R E V I E W L E T T E mentioning

confidence: 95%

“…It is a homodimer consisting of an actin-binding domain, 24 -sheet repeats, and two unstructured sequences of 32 amino acids [14]. Atomic force measurements show that, at small forces, FLNa can be modeled as a wormlike chain with a persistence length of 20 nm [15]. At higher forces of 50 -100 pN, the -sheet repeat sequences reversibly unfold, doubling the contour length [15].…”

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confidence: 99%

“…Atomic force measurements show that, at small forces, FLNa can be modeled as a wormlike chain with a persistence length of 20 nm [15]. At higher forces of 50 -100 pN, the -sheet repeat sequences reversibly unfold, doubling the contour length [15]. We use recombinant human FLNa purified from Sf9 cell lysates [16] and globular actin purified from rabbit skeletal muscle.…”

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confidence: 99%

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Stress-Dependent Elasticity of Composite Actin Networks as a Model for Cell Behavior

et al. 2006

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Section: Prl 96 088102 (2006) P H Y S I C a L R E V I E W L E T T E mentioning

confidence: 95%

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confidence: 99%

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Stress-Dependent Elasticity of Composite Actin Networks as a Model for Cell Behavior

et al. 2006

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“…The compliance of this network is dominated by the flexible cross-linkers, while the much stiffer filaments act mainly as a scaffold for the cross-linkers, ensuring rigidity of the network as a whole. Recent experiments have demonstrated that flexible biological cross-linkers such as filamin can be described as a semiflexible polymer using the wormlike chain (WLC) model [17,18]. The cross-linkers are characterized by their contour length ℓ 0 and persistence length ℓ p [15].…”

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Nonlinear Elasticity of Composite Networks of Stiff Biopolymers with Flexible Linkers

2008

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Motivated by recent experiments showing nonlinear elasticity of in vitro networks of the biopolymer actin cross-linked with filamin, we present an effective medium theory of flexibly cross-linked stiff polymer networks. We model such networks by randomly oriented elastic rods connected by flexible connectors to a surrounding elastic continuum, which self-consistently represents the behavior of the rest of the network. This model yields a cross-over from a linear elastic regime to a highly nonlinear elastic regime that stiffens in a way quantitatively consistent with experiment.PACS numbers: 87.16. Ka, 87.15. La, 82.35.Pq The mechanical response of living cells depends largely on their cytoskeleton, a network of stiff protein polymers such as F-actin, along with various associated proteins for cross-linking and force generation. In addition to their importance for cell mechanics, cytoskeletal networks have also demonstrated novel elastic properties, especially in numerous in vitro studies [1,2,3,4,5,6]. The cellular cytoskeleton, however, is an inherently composite structure, consisting of elements with highly varied mechanical properties, and there have been few theoretical or experimental studies of this aspect [8,9,10,11,12]. Recent experiments on F-actin with the physiological crosslinker filamin have demonstrated several striking features while their linear modulus is significantly lower than for rigidly cross-linked actin systems, they can nonetheless withstand remarkably large stresses and can stiffen by a factor of 1000 with applied shear [8,10,13]. This behavior appears to result from the highly flexible nature of filamin, although the basic physics of such a network, in which the elasticity is dominated by cross-linkers, is not understood. Apart from their physiological importance, such networks suggest new principles that may be extended to new synthetic materials with designed crosslinks [9].Here, we develop a theoretical model for composite networks of rigid filaments connected by flexible crosslinkers, in which the macroscopic network elasticity is governed by the cross-links. We examine this model in a limit in which the basic elastic element is a single rigid rod, directly linked by numerous compliant crosslinkers to a surrounding linear elastic medium. We show that such a network stiffens in a manner determined by the mechanics of individual cross-links, which we model both as linear springs with finite extension, and also as wormlike chains. We analyze our model in both a fully 3D network, as well as a simplified 1D representation, which already captures the essential physics of the nonlinear behavior. The finite extension ℓ 0 of the cross-links along with the length of the filaments/rods L implies that there exists a characteristic strain γ c ∼ ℓ 0 /L for the onset of the nonlinear response of the network. Indeed prior in vitro experiments, in which the length of the cross-linkers was varied [9], have reported this linear dependence on ℓ 0 . We extend this model in a fully selfconsistent man...

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“…Using atomic force microscopy 50 -220 pN have been reported; this unfolding is reversible, and the unfolded chains fold back when the external force is removed (31)(32)(33). The unfolding of the ddFLN rod was particularly interesting as one of the repeats, repeat 4, unfolded in two steps and refolded along the same pathway (33,34).…”

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Filamin-regulated F-actin Assembly Is Essential for Morphogenesis and Controls Phototaxis in Dictyostelium

Khaire

Müller

Blau-Wasser

et al. 2007

Journal of Biological Chemistry

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Dictyostelium strains lacking the F-actin cross-linking protein filamin (ddFLN) have a severe phototaxis defect at the multicellular slug stage. Filamins are rod-shaped homodimers that cross-link the actin cytoskeleton into highly viscous, orthogonal networks. Each monomer chain of filamin is comprised of an F-actin-binding domain and a rod domain. In rescue experiments only intact filamin re-established correct phototaxis in filamin minus mutants, whereas C-terminally truncated filamin proteins that had lost the dimerization domain and molecules lacking internal repeats but retaining the dimerization domain did not rescue the phototaxis defect. Deletion of individual rod repeats also changed their subcellular localization, and mutant filamins in general were less enriched at the cell cortex as compared with the full-length protein and were increasingly present in the cytoplasm. For correct phototaxis ddFLN is only required at the tip of the slug because expression under control of the cell type-specific extracellular-matrix protein A (ecmA) promoter and mixing experiments with wild type cells supported phototactic orientation. Likewise, in chimeric slugs wild type cells were primarily found at the tip of the slug, which acts as an organizer in Dictyostelium morphogenesis.

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Mechanical unfolding of single filamin A (ABP‐280) molecules detected by atomic force microscopy

Cited by 119 publications

References 24 publications

Stress-Dependent Elasticity of Composite Actin Networks as a Model for Cell Behavior

Stress-Dependent Elasticity of Composite Actin Networks as a Model for Cell Behavior

Nonlinear Elasticity of Composite Networks of Stiff Biopolymers with Flexible Linkers

Filamin-regulated F-actin Assembly Is Essential for Morphogenesis and Controls Phototaxis in Dictyostelium

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