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High-resolution Time-lapse Imaging and Automated Analysis of Microtubule Dynamics in Living Human Umbilical Vein Endothelial Cells
Published on: August 13, 2016
Distinct ECM mechanosensing pathways regulate microtubule dynamics to control endothelial cell branching
Kenneth A Myers1, Kathryn T Applegate, Gaudenz Danuser
1Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
The Journal of Cell Biology
|January 26, 2011
Summary
Microtubules link extracellular matrix (ECM) sensing to cell shape changes during blood vessel formation. Specific microtubule dynamics are regulated by ECM physical properties, guiding endothelial cell branching morphogenesis.
Area of Science:
- Cell Biology
- Biophysics
- Vascular Biology
Background:
- Endothelial cell branching morphogenesis during angiogenesis is crucial for vascular guidance.
- Physical properties of the extracellular matrix (ECM) are known to regulate this process via mechanosensing.
- The role of microtubules in connecting ECM mechanosensing to endothelial cell behavior remains unclear.
Purpose of the Study:
- To investigate the involvement of microtubules in linking ECM mechanosensing to endothelial cell branching morphogenesis.
- To determine how specific microtubule assembly dynamics are modified by and contribute to ECM mechanosensing.
Main Methods:
- Utilized a novel microtubule plus end-tracking program to analyze microtubule dynamics.
- Examined endothelial cells cultured on two-dimensional (2D) and three-dimensional (3D) ECMs with varying compliance.
- Investigated the role of myosin II contractility in mechanosensing pathways.
Main Results:
- ECM mechanosensing globally and regionally modifies microtubule assembly dynamics, specifically growth speed and persistence.
- Compliant 2D and 3D ECMs induce local differences in microtubule growth speed, dependent on myosin II contractility.
- Microtubule growth persistence is modulated by myosin II-mediated mechanosensing on 2D ECMs but not 3D ECMs.
Conclusions:
- Specific microtubule dynamics parameters are independently regulated by ECM compliance and dimensionality.
- These distinct microtubule regulation pathways are essential for guiding endothelial cell branching morphogenesis in complex ECM environments.
- Findings elucidate a novel mechanism by which physical cues from the ECM direct cytoskeletal organization for vascular development.
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