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On the origin of microtubules’ high-pressure sensitivity

DOI: 10.1016/j.bpj.2018.01.021 DOI Help

Authors: Mimi Gao (Technische Universität Dortmund) , Melanie Berghaus (Technische Universität Dortmund) , Simone Möbitz (Technische Universität Dortmund) , Vitor Schuabb (Technische Universität Dortmund) , Nelli Erwin (Technische Universität Dortmund) , Marius Herzog (Technische Universität Dortmund) , Karin Julius (Technische Universität Dortmund) , Christian Sternemann (Technische Universität Dortmund) , Roland Winter (Technische Universität Dortmund)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Biophysical Journal , VOL 114 , PAGES 1080 - 1090

State: Published (Approved)
Published: March 2018
Diamond Proposal Number(s): 14949

Abstract: For over 50 years, it has been known that the mitosis of eukaryotic cells is inhibited already at high hydrostatic pressure conditions of 30 MPa. This effect has been attributed to the disorganization of microtubules, the main component of the spindle apparatus. However, the structural details of the depolymerization and the origin of the pressure sensitivity have remained elusive. It has also been a puzzle how complex organisms could still successfully inhabit extreme high-pressure environments such as those encountered in the depth of oceans. We studied the pressure stability of microtubules at different structural levels and for distinct dynamic states using high-pressure Fourier-transform infrared spectroscopy and Synchrotron small-angle x-ray scattering. We show that microtubules are hardly stable under abyssal conditions, where pressures up to 100 MPa are reached. This high-pressure sensitivity can be mainly attributed to the internal voids and packing defects in the microtubules. In particular, we show that lateral and longitudinal contacts feature different pressure stabilities, and they define also the pressure stability of tubulin bundles. The intactness of both contact types is necessary for the functionality of microtubules in vivo. Despite being known to dynamically stabilize microtubules and prevent their depolymerization, we found that the anti-cancer drug taxol and the accessory protein MAP2c decrease the pressure stability of microtubule protofilaments. Moreover, we demonstrate that the cellular environment itself is a crowded place and accessory proteins can increase the pressure stability of microtubules and accelerate their otherwise highly pressure-sensitive de novo formation.

Subject Areas: Biology and Bio-materials

Instruments: I22-Small angle scattering & Diffraction

Other Facilities: BL9 at DELTA

Added On: 19/03/2018 09:31

Discipline Tags:

Structural biology Biophysics Life Sciences & Biotech

Technical Tags:

Scattering Small Angle X-ray Scattering (SAXS)