Optogenetic control of cellular forces and mechanotransduction
Léo Valon1, Ariadna Marín-Llauradó1, Thomas Wyatt2,3
1Institute for Bioengineering of Catalonia, Barcelona 08028, Spain.
Nature Communications
|February 11, 2017
Summary
Scientists developed optogenetic tools to precisely control cellular forces using light. This technology allows researchers to manipulate cell migration, division, and tissue development by targeting RhoA activation with high accuracy.
Area of Science:
- Cell Biology
- Biophysics
- Optogenetics
Background:
- Cellular contractile forces are crucial for fundamental biological processes like migration, division, and tissue development.
- Existing methods for controlling these forces lack precise spatiotemporal accuracy.
- Understanding the regulation of cellular contractility is key to addressing diseases such as cancer.
Purpose of the Study:
- To develop novel optogenetic tools for precise spatiotemporal control of cellular contractile forces.
- To investigate the effects of localized RhoA activation on cellular mechanics and mechanotransduction.
- To provide a new method for studying cell migration, division, and tissue morphogenesis.
Main Methods:
- Engineered a light-gated dimerizer system (CRY2/CIBN) to control the subcellular activation of RhoA.
- Fused the RhoA activator ARHGEF11 catalytic domain to CRY2-mCherry (optoGEF-RhoA).
- Targeted optoGEF-RhoA to either the plasma membrane or mitochondrial membrane via CIBN binding partners.
Main Results:
- Light-induced translocation of optoGEF-RhoA to the plasma membrane rapidly increased cellular traction, intercellular tension, and tissue compaction.
- Translocation to mitochondria induced opposite changes in these physical properties.
- Modifications in cellular contractility were paralleled by changes in YAP nuclear localization, indicating control over mechanotransduction.
Conclusions:
- The developed optogenetic tools enable precise spatiotemporal regulation of cellular forces.
- This technology offers a powerful method to study the role of contractility in various cellular processes.
- The approach allows for the investigation of mechanotransduction pathways with unprecedented temporal and spatial control.
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