Tubulin: from atomistic structure to supramolecular mechanical properties

Deriu, Marco Agostino; Enemark, Søren; Soncini, Monica; Montevecchi, Franco Maria; Redaelli, Alberto

doi:10.1007/s10853-007-1784-6

Cited by 47 publications

(47 citation statements)

References 19 publications

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“…In particular, a typical limit of the SMD simulations concerns the pulling rate, which is usually dictated by the size of the molecular systems. The lowest pulling rate used in the present experiment was 0.0001 nm Á ps À1 , which is comparable to the one adopted in previous computational studies [10,25,26] but still higher than the pulling rates used regularly in AFM experiments, [15] which vary in the nm Á ms À1 range.…”

Section: Resultssupporting

confidence: 79%

Mechanical Characterization of Motor Proteins: A Molecular Dynamics Approach

Aprodu

Soncini

Redaelli

2008

Macro Theory & Simulations

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A new approach, based on molecular dynamics, is presented to measure the mechanical properties of motor proteins, which are important for accomplishing their intracellular functions. Two different set‐ups were designed to mimic the optical tweezers and surface force apparatus experiments. The results obtained show that the stiffness and elastic modulus of kinesin motor domain are 377 pN · nm−1 and 0.17 GPa, respectively, while the myosin motor domain is characterized by a stiffness of 271 pN · nm−1 and an elastic modulus of 0.26 GPa. These results suggest that the source of the very low stiffness detected for full‐length molecules is located outside of the globular part of the proteins.

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Section: Resultssupporting

confidence: 79%

Mechanical Characterization of Motor Proteins: A Molecular Dynamics Approach

Aprodu

Soncini

Redaelli

2008

Macro Theory & Simulations

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“…Based on these simulation results, as the deformation of the MT lattice is affine, which holds at small deformation, it is valid to use identical bond stiffness parameters for both intra-and inter-dimer bonds. There is also a difference between lateral α-α and β-β interactions, which is 15 and 11 N/m, respectively [38]. Considering ε α−α =0.277 eV, ε β−β =0.203 eV, and the averaged value ε=0.237 eV, we also find very close results in these simulations.…”

Section: Parameters In Interaction Energy Functionalssupporting

confidence: 74%

“…Finally, we obtain ε=0.237 eV by fitting to k S in [34]. According to atomistic simulations by Deriu et al [38], the intra-dimer interaction coefficient 45 N/m is 2.5 times larger than the inter-dimer interactions 18 N/m. With a spring-bead chain model, we obtain k intra =5.911 eV/nm and k inter =2.364 eV/nm, while k T =3.378 eV/nm if we neglect the difference.…”

Section: Parameters In Interaction Energy Functionalsmentioning

confidence: 85%

“…After Nogales et al [4] resolve the detailed atomic structure of MT tubulin dimers (PDB ID: 1TUB) in 1998, a bottomup understanding of MTs becomes possible and numerous experimental and theoretical studies thus are initialized. Deriu et al [38] build a mesoscale model of α-and β-tubulin monomers and dimers based on the atomic structures 1TUB. Molecular simulations are performed to calculate inner-dimer and inter-dimer interactions, and the lateral interactions between α-α and β-β tubulins without considering thermal fluctuation.…”

Section: Introductionmentioning

confidence: 99%

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Mechanics of Microtubules from a Coarse-Grained Model

2011

BioNanoSci.

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We develop a coarse-grained model for the microtubule (MT) based on its α and β subunits and many-body interactions between them. Thermodynamic and mechanical properties of MTs are investigated using this model by performing molecular dynamics (MD) simulations, which is validated by reproducing basic mechanical properties of MTs in consistence with experiments. Based on simulations results, phenomena observed such as the length dependence of persistence length, mechanically induced disaggregation, and coupling between bending, shear, and twisting deformation are discussed. The simple model presented here lays the ground for further exploration of MTs mechanics and cellular energetics where MTs are involved.

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“…This suggests that in the dry microfibril the deformation mechanism initially involves primarily the straightening of the collagen molecules and not stretching of the molecules itself (this is confirmed by the observation that the end-to-end distance at 200 MPa stress is 260 nm, much shorter than the collagen molecules' contour length). The analysis of the gap/overlap ratio (red, panel c) shows that the deformation is initially distributed in both the gap and [71][72][73][74][75]. However, most of the protein materials feature Young's moduli in the range of 100 MPa to 10 GPa, well below the stiffness of many synthetic nanostructured material such as carbon nanotubes.…”

Section: Structures In Pdb Formatmentioning

confidence: 99%

Hierarchical Structure and Nanomechanics of Collagen Microfibrils from the Atomistic Scale Up

Gautieri

Vesentini²,

Redaelli³

et al. 2011

Nano Lett.

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590

488

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Abstract:Collagen constitutes one third of the human proteome, providing mechanical stability, elasticity and strength to connective tissues. Collagen is also the dominating material in the extracellular matrix (ECM) and is thus crucial for cell differentiation, growth and pathology. However, fundamental questions remain with respect to the origin of the unique mechanical properties of collagenous tissues, and in particular its stiffness, extensibility and nonlinear mechanical response. By using x-ray diffraction data of a collagen fibril reported by Orgel et al.(Proceedings of the National Academy of Sciences USA, 2006) in combination with protein structure identification methods, here we present an experimentally validated model of the nanomechanics of a collagen microfibril that incorporates the full biochemical details of the amino acid sequence of the constituting molecules. We report the analysis of its mechanical properties under different levels of stress and solvent conditions, using a full-atomistic force field including explicit water solvent. Mechanical testing of hydrated collagen microfibrils yields a Young's modulus of ≈300 MPa at small and ≈1.2 GPa at larger deformation in excess of 10% strain, in excellent agreement with experimental data. Dehydrated, dry collagen microfibrils show a significantly increased Young's modulus of ≈1.8 to 2.25 GPa (or ≈6.75 times the modulus in the wet state) owing to a much tighter molecular packing, in good agreement with experimental measurements (where an increase of the modulus by ≈9 times was found). Our model demonstrates that the unique mechanical properties of collagen microfibrils can be explained based on their hierarchical structure, where deformation is mediated through mechanisms that operate at different hierarchical levels. Key mechanisms involve straightening of initially disordered and helically twisted molecules at small strains, followed by axial stretching of molecules, and eventual molecular uncoiling at extreme deformation. These mechanisms explain the striking difference of the modulus of collagen fibrils compared with single molecules, which is found in the range of 4.8±2 GPa or ≈10-20 times greater. These findings corroborate the notion that collagen tissue properties are highly scale dependent and nonlinear elastic, an issue that must be considered in the development of models that describe the interaction of cells with collagen in the extracellular matrix. A key impact the atomistic model of collagen microfibril mechanics reported here is that it enables the bottom-up elucidation of structure-property relationships in the broader class of collagen materials such as tendon or bone, including studies in the context of genetic disease where the incorporation of biochemical, genetic details in material models of connective tissue is essential.

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Tubulin: from atomistic structure to supramolecular mechanical properties

Cited by 47 publications

References 19 publications

Mechanical Characterization of Motor Proteins: A Molecular Dynamics Approach

Mechanical Characterization of Motor Proteins: A Molecular Dynamics Approach

Mechanics of Microtubules from a Coarse-Grained Model

Hierarchical Structure and Nanomechanics of Collagen Microfibrils from the Atomistic Scale Up

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