Actin-binding proteins sensitively mediate F-actin bundle stiffness

Claessens, Mireille Maria Anna Elisabeth; Bathe, Mark; Frey, Erwin; Bausch, Andreas R.

doi:10.1038/nmat1718

Cited by 247 publications

(308 citation statements)

References 38 publications

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“…The deformations are undulatory in nature and may be expressed by ⌬ Ӎ r 3/2 / P 1/2 . 32,52,53 On the whole, we conclude that the mechanical limit breaks down as r approaches P. For the widest channels in Table II and III, the predictions for g must be considered to be tentative only, for this reason. Complete analyses of the global persistence length including fluctuations have been given for chains in the nematic state.…”

Section: Discussionmentioning

confidence: 80%

DNA confined in nanochannels: Hairpin tightening by entropic depletion

Odijk

2006

The Journal of Chemical Physics

217

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A theory is presented of the elongation of double-stranded DNA confined in a nanochannel based on a study of the formation of hairpins. A hairpin becomes constrained as it approaches the wall of a channel which leads to an entropic force causing the hairpin to tighten. The DNA in the hairpin remains double-stranded. The free energy of the hairpin is significantly larger than what one would expect if this entropic effect were unimportant. As a result, the distance between hairpins or the global persistence length is often tens of micrometer long and may even reach millimeter sizes for 10 nm thin channels. The hairpin shape and size and the DNA elongation are computed for nanoslits and circular and square nanochannels. A comparison with experiment is given.

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Section: Discussionmentioning

confidence: 80%

DNA confined in nanochannels: Hairpin tightening by entropic depletion

Odijk

2006

The Journal of Chemical Physics

217

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“…It has a molecular mass of B55 kDa, functions as a monomer and is required to maximally cross-link the actin filaments into straight, compact and rigid bundles, to impart distinct mechanical stiffness to actin bundles 26,27 . Fascin holds 10-30 parallel actin filaments together to form filopodia 60-200 nm in diameter 13 .…”

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confidence: 99%

Targeted inhibition of fascin function blocks tumour invasion and metastatic colonization

et al. 2015

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One of the key steps during tumour metastasis is tumour cell migration and invasion, which require actin cytoskeletal reorganization. Among the critical actin cytoskeletal protrusion structures are the filopodia, which act like cell sensory organs to communicate with the extracellular microenvironment and participate in fundamental cell functions such as cell adhesion, spreading and migration in the three-dimensional environment. Fascin is the main actin-bundling protein in filopodia. Using high-throughput screening, here we identify and characterize small molecules that inhibit the actin-bundling activity of fascin. Focusing on one such inhibitor, we demonstrate that it specifically blocks filopodial formation, tumour cell migration and invasion in vitro, and metastasis in vivo. Hence, target-specific anti-fascin agents have a therapeutic potential for cancer treatment.

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“…Significant progress has also been made towards the description of the collective properties of WLCs, for example, in the form of entangled solutions. One of the hallmarks of this development is the scaling of the plateau shear modulus with concentration G c 7=5 [7][8][9], which is well established experimentally [10,11].Another important emerging class of semiflexible polymers consists of bundles of WLCs [12,13]. Semiflexible polymer bundles consisting of F-actin or microtubules are ubiquitous in biology [14] and have unique mechanical properties that may well be exploited in the design of nanomaterials [13].…”

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confidence: 99%

“…Additional experiments [12,13,21,30] are required to test the applicability of the derived results to biological and synthetic bundles.…”

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confidence: 99%

Statistical Mechanics of Semiflexible Bundles of Wormlike Polymer Chains

2007

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We demonstrate that a semiflexible bundle of wormlike chains exhibits a state-dependent bending stiffness that alters fundamentally its scaling behavior with respect to the standard wormlike chain. We explore the equilibrium conformational and mechanical behavior of wormlike bundles in isolation, in cross-linked networks, and in solution. DOI: 10.1103/PhysRevLett.99.048101 PACS numbers: 87.16.Ka, 82.35.Lr, 83.10.ÿy, 87.15.La In recent decades, the wormlike chain (WLC) has emerged as the standard model for the description of semiflexible polymers [1]. The defining property of a WLC is a mechanical bending stiffness f that is an intrinsic material constant of the polymer. Within this framework, numerous correlation and response functions have been calculated, providing a comprehensive picture of the equilibrium and dynamical properties of WLCs [2 -4]. A number of experimental studies have demonstrated the applicability of the WLC model to DNA [5] and F-actin [6], among other biological and synthetic polymers. Significant progress has also been made towards the description of the collective properties of WLCs, for example, in the form of entangled solutions. One of the hallmarks of this development is the scaling of the plateau shear modulus with concentration G c 7=5 [7][8][9], which is well established experimentally [10,11].Another important emerging class of semiflexible polymers consists of bundles of WLCs [12,13]. Semiflexible polymer bundles consisting of F-actin or microtubules are ubiquitous in biology [14] and have unique mechanical properties that may well be exploited in the design of nanomaterials [13]. As shown by Bathe et al. [15,16], wormlike bundles (WLBs) have a state-dependent bending stiffness B that derives from a generic interplay between the high stiffness of individual filaments and their rather soft relative sliding motion. In this Letter, we demonstrate that this state dependence gives rise to fundamentally new behavior that cannot be reproduced trivially using existing relations for WLCs. We explore the consequences of a state-dependent bending stiffness on the statistical mechanics of isolated WLBs, as well as on the scaling behavior of their entangled solutions and cross-linked networks.We consider the bending of ordered bundles with an isotropic cross section. A bundle consists of N filaments of length L and bending stiffness f . Filaments are irreversibly cross-linked to their nearest neighbors by discrete cross-links with mean axial spacing . Cross-links are modeled to be compliant in shear along the bundle axis with finite shear stiffness k and to be inextensible transverse to the bundle axis, thus fixing the interfilament distance b [17]. Bundle deformations are characterized by the transverse deflection r ? s of the bundle neutral surface at axial position s along the backbone and by the stretching deformation u i s of filament i. The torsional stiffness of the bundle is assumed to be of the same order as the bending stiffness. Thus, as long as transverse deflections remain sm...

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Actin-binding proteins sensitively mediate F-actin bundle stiffness

Cited by 247 publications

References 38 publications

DNA confined in nanochannels: Hairpin tightening by entropic depletion

DNA confined in nanochannels: Hairpin tightening by entropic depletion

Targeted inhibition of fascin function blocks tumour invasion and metastatic colonization

Statistical Mechanics of Semiflexible Bundles of Wormlike Polymer Chains

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