Microtubule dynamics regulate cyclic stretch-induced cell alignment in human airway smooth muscle cells

Masataka Morioka, Harikrishnan Parameswaran, Keiji Naruse, Masashi Kondo, Masahiro Sokabe, Yoshinori Hasegawa, Béla Suki, Satoru Ito

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Abstract

Microtubules are structural components of the cytoskeleton that determine cell shape, polarity, and motility in cooperation with the actin filaments. In order to determine the role of microtubules in cell alignment, human airway smooth muscle cells were exposed to cyclic uniaxial stretch. Human airway smooth muscle cells, cultured on type I collagen-coated elastic silicone membranes, were stretched uniaxially (20% in strain, 30 cycles/min) for 2 h. The population of airway smooth muscle cells which were originally oriented randomly aligned near perpendicular to the stretch axis in a time-dependent manner. However, when the cells treated with microtubule disruptors, nocodazole and colchicine, were subjected to the same cyclic uniaxial stretch, the cells failed to align. Lack of alignment was also observed for airway smooth muscle cells treated with a microtubule stabilizer, paclitaxel. To understand the intracellular mechanisms involved, we developed a computational model in which microtubule polymerization and attachment to focal adhesions were regulated by the preexisting tensile stress, pre-stress, on actin stress fibers. We demonstrate that microtubules play a central role in cell re-orientation when cells experience cyclic uniaxial stretching. Our findings further suggest that cell alignment and cytoskeletal reorganization in response to cyclic stretch results from the ability of the microtubule-stress fiber assembly to maintain a homeostatic strain on the stress fiber at focal adhesions. The mechanism of stretch-induced alignment we uncovered is likely involved in various airway functions as well as in the pathophysiology of airway remodeling in asthma.

Original languageEnglish
Article numbere26384
JournalPloS one
Volume6
Issue number10
DOIs
Publication statusPublished - 17-10-2011

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Morioka, M., Parameswaran, H., Naruse, K., Kondo, M., Sokabe, M., Hasegawa, Y., Suki, B., & Ito, S. (2011). Microtubule dynamics regulate cyclic stretch-induced cell alignment in human airway smooth muscle cells. PloS one, 6(10), [e26384]. https://doi.org/10.1371/journal.pone.0026384