Microtubules are hollow cylindrical polymers of the protein tubulin that play a number of important dynamic and structural roles in eukaryotic cells. Both in vivo and in vitro microtubules can exist in several possible configurations, differing in the number of protofilaments, helical rise of tubulin dimers, and protofilament skew angle with respect to the main tube axis. Here, finite element modeling is applied to examine the mechanical response of several known microtubule types when subjected to radial deformation. The data presented here provide an important insight into microtubule stiffness and reveal that protofilament orientation does not affect radial stiffness. Rather, stiffness is primarily dependent on the effective Young's modulus of the polymerized material and the effective radius of the microtubule. These results are also directly correlated to atomic force microscopy nanoindentation measurements to allow a more detailed interpretation of previous experiments. When combined with experimental data that show a significant difference between microtubules stabilized with a slowly hydrolyzable GTP analog and microtubules stabilized with paclitaxel, the finite element data suggest that paclitaxel increases the overall radial flexibility of the microtubule wall.
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http://dx.doi.org/10.1016/j.bpj.2010.06.065 | DOI Listing |
Nano Lett
January 2025
Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
Microtubules (MTs) are dynamic cytoskeletal polymers essential for mediating fundamental cellular processes, including cell division, intracellular transport, and cell shape maintenance. Understanding the arrangement of tubulin heterodimers within MTs is key to their function. Using frequency modulation atomic force microscopy (FM-AFM) and simulations, we revealed the submolecular arrangement of α- and β-tubulin subunits on the inner MT surface.
View Article and Find Full Text PDFNature
July 2024
Astbury Centre for Structural Molecular Biology, School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, UK.
A defining pathological feature of most neurodegenerative diseases is the assembly of proteins into amyloid that form disease-specific structures. In Alzheimer's disease, this is characterized by the deposition of β-amyloid and tau with disease-specific conformations. The in situ structure of amyloid in the human brain is unknown.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
June 2024
Bavarian Nuclear Magnetic Resonance Center at the Department of Biosciences, School of Natural Sciences, Technische Universität München, Garching 85747, Germany.
Proteins
March 2024
Center of Functional Protein Assemblies, Technical University of Munich, Garching, Germany.
Self-assembled aggregation of peptides and proteins into regular amyloid fibrils is associated with several neurodegenerative diseases. In case of Alzheimer's disease proteolytic cleavage products of the amyloid precursor protein form pathological amyloid-beta fibrils in a nucleation and propagation phase. The molecular details and thermodynamic driving forces of amyloid formation are not well understood, but are of high relevance for potential pharmacological interference.
View Article and Find Full Text PDFData Brief
February 2024
Institute of Photonics and Electronics of the Czech Academy of Sciences, Prague, 18200, Czechia.
We present trajectories from non-equilibrium (in electric field) molecular dynamics (MD) simulations of a kinesin motor domain on tubulin heterodimers with two tubulin heterodimers forming neighbouring microtubule protofilaments. The trajectories are for no field (long equilibrium simulation), for four different electric field orientations (X, -X, Y, -Y) and for the X electric field at four different field strengths. We also provide a trajectory for larger simulation box.
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