Molecular Modeling of the Axial and Circumferential Elastic Moduli of Tubulin

Zeiger, Adam S.; Layton, Bradley E.

doi:10.1529/biophysj.108.131359

Cited by 23 publications

(18 citation statements)

References 59 publications

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“…Our model of OMP elasticity also provides a value of Young’s modulus larger than those measured for other structural elements found in biology, such as bacterial capsids (~2 GPa) and microtubules (~1 GPa). 21–22, 44 Finally, OMPs demonstrate similar elastic properties to materials proposed to derive their elasticity from β-sheet secondary structure, such as spider silk. 18 The similarities between the values of E for spider silk and OMPs provided a starting point for the second half of our analysis.…”

Section: Resultsmentioning

confidence: 90%

Building Blocks of the Outer Membrane: Calculating a General Elastic Energy Model for β-Barrel Membrane Proteins

Lessen

Fleming

et al. 2018

J. Chem. Theory Comput.

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The outer membranes of Gram negative bacteria are the first points of contact these organisms make with their environment. Understanding how composition determines the mechanical properties of this essential barrier is of paramount importance. Therefore, we developed a new computational method to measure the elasticity of transmembrane proteins found in the outer membrane. Using all-atom molecular dynamics simulations of these proteins, we apply a set of external forces to mechanically stress the transmembrane β-barrels. Our results from four representative β-barrels show that outer membrane proteins display elastic properties that are approximately 70 to 190 times stiffer than neat lipid membranes. These findings suggest that outer membrane β-barrels are a significant source of mechanical stability in bacteria. Our all-atom approach further reveals that resistance to radial stress is encoded by a general mechanism that includes stretching of backbone hydrogen bonds and tilting of β-strands with respect to the bilayer normal. This computational framework facilitates an increased theoretical understanding of how varying lipid and protein amounts affect the mechanical properties of the bacterial outer membrane.

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Section: Resultsmentioning

confidence: 90%

Building Blocks of the Outer Membrane: Calculating a General Elastic Energy Model for β-Barrel Membrane Proteins

Lessen

Fleming

et al. 2018

J. Chem. Theory Comput.

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“…Other studies have used molecular mechanics techniques to perform tensile tests on the tubulin monomer [23], and more complete studies using hybrid molecular dynamics or finite element modeling have been applied to study mechanosensitive ion channels [24]. The coarse-graining techniques developed here are similar to a large number of bead-spring models that have been developed to describe biomolecular systems (see [25] for a nice summary of current approaches).…”

Section: Prl 104 018101 (2010) P H Y S I C a L R E V I E W L E T T Ementioning

confidence: 99%

Microtubule Elasticity: Connecting All-Atom Simulations with Continuum Mechanics

Sept

MacKintosh

2010

Phys. Rev. Lett.

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The mechanical properties of microtubules have been extensively studied using a wide range of biophysical techniques, seeking to understand the mechanics of these cylindrical polymers. Here we develop a method for connecting all-atom molecular dynamics simulations with continuum mechanics and show how this can be applied to understand microtubule mechanics. Our coarse-graining technique applied to the microscopic simulation system yields consistent predictions for the Young's modulus and persistence length of microtubules, while clearly demonstrating how binding of the drug Taxol decreases the stiffness of microtubules. The techniques we develop should be widely applicable to other macromolecular systems. DOI: 10.1103/PhysRevLett.104.018101 PACS numbers: 87.16.Ka, 83.10.Ày, 87.15.AÀ, 87.15.La Microtubules are essential players in a wide range of cellular functions. The protein tubulin polymerizes to form these filaments resulting in a hollow cylinder with a diameter of about 25 nm and lengths that range from tens of nanometers to tens of microns. Microtubules are the most rigid structures within the cell and their mechanical stability is particularly important for the role that microtubules play in cell division, cellular transport, and their basic ability to help provide cell shape. The mechanical properties of purified microtubules have been studied extensively using many biophysical techniques, including atomic force microscopy, thermal bending, and single molecule techniques [1][2][3][4][5][6][7][8][9][10][11]. Since microtubules are dynamic polymers and have intrinsic instability, many of these experimental studies have been performed on Taxol-stabilized microtubules, although the mechanical consequences of the drug Taxol for microtubule mechanics remains unclear. The majority of studies have found that the addition of Taxol results in ''softer'' microtubules with a shorter persistence length and lower Young's modulus [1][2][3][4][5], while one published study had found the opposite result [6]. Recently, even the standard elastic model of microtubules characterized by a single elastic bending constant has been called into question by reports of length-dependent stiffness [12]. Thus, in spite of decades of experimental study, many basic questions and puzzles remain concerning the mechanics of even individual microtubules in vitro, let alone in vivo.Here, we combine all-atom simulations and continuum elastic modeling in order to determine both the elastic parameters of persistence length and Young's modulus, as well as to test the applicability of simple, continuum shell elasticity for microtubules. Based on a molecular dynamics simulation of a small section of six tubulin monomers [13], we show that the observed fluctuations of this section are consistent with linear elastic constants for both bending and stretching along the microtubule axis.From these measurements, we determine the effective elastic properties for the microtubule wall, treated as an elastic sheet. With the addition of Taxol, we find in...

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“…The monomers, a-tub (440 residues) and b-tub (427 residues), have very similar structures consisting of a N-terminal nucleotide (GTP or GDP) binding domain, an intermediate taxol binding domain (in b-tub), and a C-terminal microtubule-associated protein binding domain comprising residues 1-205, 206-381, and 382-440, respectively (15). The mechanical properties of MTs play a crucial role in cell division and matrix remodeling induced by mechanical loading (16)(17)(18)(19). Understanding the microscopic principles governing MT instability (7,13) and breaking of the (-) end from the centrosome, which are relevant also for axonal guidance in new directions (20), is therefore vital for understanding basic cellular processes.…”

Section: Introductionmentioning

confidence: 99%

Exploring the Contribution of Collective Motions to the Dynamics of Forced-Unfolding in Tubulin

Joshi

Momin

Haines

et al. 2010

Biophysical Journal

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Decomposition of the intrinsic dynamics of proteins into collective motions among distant regions of the protein structure provides a physically appealing approach that couples the dynamics of the system with its functional role. The cellular functions of microtubules (an essential component of the cytoskeleton in all eukaryotic cells) depend on their dynamic instability, which is altered by various factors among which applied forces are central. To shed light on the coupling between forces and the dynamic instability of microtubules, we focus on the investigation of the response of the microtubule subunits (tubulin) to applied forces. We address this point by adapting an approach designed to survey correlations for the equilibrium dynamics of proteins to the case of correlations for proteins forced-dynamics. The resulting collective motions in tubulin have a number of functional implications, such as the identification of long-range couplings with a role in blocking the dynamic instability of microtubules. A fundamental implication of our study for the life of a cell is that, to increase the likelihood of unraveling of large cytoskeletal filaments under physiological forces, molecular motors must use a combination of pulling and torsion rather than just pulling.

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Molecular Modeling of the Axial and Circumferential Elastic Moduli of Tubulin

Cited by 23 publications

References 59 publications

Building Blocks of the Outer Membrane: Calculating a General Elastic Energy Model for β-Barrel Membrane Proteins

Building Blocks of the Outer Membrane: Calculating a General Elastic Energy Model for β-Barrel Membrane Proteins

Microtubule Elasticity: Connecting All-Atom Simulations with Continuum Mechanics

Exploring the Contribution of Collective Motions to the Dynamics of Forced-Unfolding in Tubulin

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