Distinct ECM mechanosensing pathways regulate microtubule dynamics to control endothelial cell branching morphogenesis

Kenneth A. Myers, Kathryn T. Applegate, Gaudenz Danuser, Robert S. Fischer, Clare M. Waterman

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

During angiogenesis, cytoskeletal dynamics that mediate endothelial cell branching morphogenesis during vascular guidance are thought to be regulated by physical attributes of the extracellular matrix (ECM) in a process termed mechanosensing. Here, we tested the involvement of microtubules in linking mechanosensing to endothelial cell branching morphogenesis. We used a recently developed microtubule plus end-tracking program to show that specific parameters of microtubule assembly dynamics, growth speed and growth persistence, are globally and regionally modified by, and contribute to, ECM mechanosensing. We demonstrated that engagement of compliant two-dimensional or three-dimensional ECMs induces local differences in microtubule growth speed that require myosin II contractility. Finally, we found that microtubule growth persistence is modulated by myosin II-mediated compliance mechano-sensing when cells are cultured on two-dimensional ECMs, whereas three-dimensional ECM engagement makes microtubule growth persistence insensitive to changes in ECM compliance. Thus, compliance and dimensionality ECM mechanosensing pathways independently regulate specific and distinct microtubule dynamics parameters in endothelial cells to guide branching morphogenesis in physically complex ECMs.

Original languageEnglish (US)
Pages (from-to)321-334
Number of pages14
JournalJournal of Cell Biology
Volume192
Issue number2
DOIs
StatePublished - Jan 24 2011

ASJC Scopus subject areas

  • Cell Biology

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