Mechanosensing Controlled Directly by Tyrosine Kinases

Bo Yang, Zi Zhao Lieu, Haguy Wolfenson, Feroz M. Hameed, Alexander D. Bershadsky, Michael Sheetz

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

To understand how cells form tissues, we need to understand how the tyrosine kinases are involved in controlling cell mechanics, whether they act directly as parts of mechanosensing machines or indirectly. Cells test the critical parameter of matrix rigidity by locally contracting ("pinching") matrices and measuring forces, and the depletion of contractile units causes transformation. We report here that knocking down the receptor tyrosine kinases (RTKs), AXL, and ROR2, alters rigidity sensing and increases the magnitude or duration of local contraction events, respectively. Phospho-AXL and ROR2 localize to contraction units and bind major contractile components, tropomyosin 2.1 (AXL), myosin IIA (AXL), and filamin A (ROR2). At a molecular level, phosphorylated AXL localizes to active myosin filaments and phosphorylates tropomyosin at a tyrosine critical for adhesion formation. ROR2 binding of ligand is unnecessary, but binding filamin A helps function. Thus, AXL and ROR2 alter rigidity sensing and consequently morphogenic processes by directly controlling local mechanosensory contractions without ligands.

Original languageEnglish (US)
Pages (from-to)5951-5961
Number of pages11
JournalNano Letters
Volume16
Issue number9
DOIs
StatePublished - Sep 14 2016
Externally publishedYes

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Keywords

  • AXL
  • mechanotransduction
  • nano pillars
  • protein tyrosine kinases
  • Rigidity sensing
  • ROR2

ASJC Scopus subject areas

  • Bioengineering
  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanical Engineering

Cite this

Yang, B., Lieu, Z. Z., Wolfenson, H., Hameed, F. M., Bershadsky, A. D., & Sheetz, M. (2016). Mechanosensing Controlled Directly by Tyrosine Kinases. Nano Letters, 16(9), 5951-5961. https://doi.org/10.1021/acs.nanolett.6b02995