Biomechanics of actin filaments: A computational multi-level study

“…31 More recently, the extensional and torsional stiffness of undecorated actin filaments have been evaluated using MD simulations. 34,35 These studies demonstrate how local conformational changes can propagate to affect macroscopic filament properties.…”

Section: Introductionmentioning

confidence: 85%

“…27,31–35 Chu and Voth 32 investigated how the persistence length of undecorated actin filaments varies with changes in D-loop conformation using molecular dynamics (MD) simulations. Pfaendtner et al 33 refined this study using improved filament structures 36 and found that unfolding of the D-loop increased the persistence length regardless of the state of the bound nucleotide.…”

Section: Introductionmentioning

confidence: 99%

Molecular Origins of Cofilin-Linked Changes in Actin Filament Mechanics

Fan

Saunders

Haddadian

et al. 2013

Journal of Molecular Biology

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The actin regulatory protein cofilin plays a central role in actin assembly dynamics by severing filaments and increasing the concentration of ends from which subunits add and dissociate. Cofilin binding modifies the average structure and mechanical properties of actin filaments, thereby promoting fragmentation of partially decorated filaments at boundaries of bare and cofilin-decorated segments. Despite extensive evidence for cofilin-dependent changes in filament structure and mechanics, it is unclear how the two processes are linked at the molecular level. Here, we use molecular dynamics simulations and coarse-grained analyses to evaluate the molecular origins of the changes in filament compliance due to cofilin binding. Filament subunits with bound cofilin are less flat and maintain a significantly more open nucleotide cleft than bare filament subunits. Decorated filament segments are less twisted, thinner (considering only actin), and less connected than their bare counterparts, which lowers the filament bending persistence length and torsional stiffness. Using coarse-graining as an analysis method reveals that cofilin binding increases the average distance between the adjacent long-axis filament subunit, thereby weakening their interaction. In contrast, a fraction of lateral filament subunit contacts are closer and presumably stronger with cofilin binding. A cofilactin interface contact identified by cryo-electron microscopy is unstable during simulations carried out at 310K, suggesting that this particular interaction may be short-lived at ambient temperatures. These results reveal the molecular origins of cofilin-dependent changes in actin filament mechanics that may promote filament severing.

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“…In Bathe (2008), MD data are used to define the protein volume, effective mass density, and boundary conditions. Additionally, the mechanical properties of actin filament rearranged by MD simulation were investigated based on the normal mode analysis (Deriu et al 2011). In contrast, the knowledge from MD was often applied to various coarse-grained models for a large amount of calculation.…”

Section: Application Of MD Methods To Actin Filamentsmentioning

confidence: 99%

Multiscale modeling and mechanics of filamentous actin cytoskeleton

Yamaoka

Matsushita

Shimada

et al. 2011

Biomech Model Mechanobiol

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The adaptive structure and functional changes of the actin cytoskeleton are induced by its mechanical behavior at various temporal and spatial scales. In particular, the mechanical behaviors at different scales play important roles in the mechanical functions of various cells, and these multiscale phenomena require clarification. To establish a milestone toward achieving multiscale modeling and simulation, this paper reviews mathematical analyses and simulation methods applied to the mechanics of the filamentous actin cytoskeleton. The actin cytoskeleton demonstrates characteristic behaviors at every temporal and spatial scale, and mathematical models and simulation methods can be applied to each level of actin cytoskeletal structure ranging from the molecular to the network level. This paper considers studies on mathematical models and simulation methods based on the molecular dynamics, coarse-graining, and continuum dynamics approaches. Every temporal and spatial scale of actin cytoskeletal structure is considered, and it is expected that discrete and continuum dynamics ranging from functional expression at the molecular level to macroscopic functional expression at the whole cell level will be developed and applied to multiscale modeling and simulation.

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Biomechanics of actin filaments: A computational multi-level study

Cited by 33 publications

References 65 publications

Aberrant movement of β-tropomyosin associated with congenital myopathy causes defective response of myosin heads and actin during the ATPase cycle

Aberrant movement of β-tropomyosin associated with congenital myopathy causes defective response of myosin heads and actin during the ATPase cycle

Molecular Origins of Cofilin-Linked Changes in Actin Filament Mechanics

Multiscale modeling and mechanics of filamentous actin cytoskeleton

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