Optogenetic manipulation of cellular communication using engineered myosin motors

Area of Science:

• Cell Biology
• Optogenetics
• Regenerative Medicine

Background:

• Cellular projections like neurites and filopodia are crucial for cell communication.
• Existing tools lack precision in manipulating the composition and dynamics of these extensions.
• Controlling cellular projections is key to understanding and influencing biological processes.

Purpose of the Study:

• To develop a novel optogenetic toolbox for precise manipulation of cellular projections.
• To enable selective transport of cargo within cellular extensions using light-inducible motors.
• To investigate the role of filopodial extensions in axolotl limb regeneration.

Main Methods:

• Engineered artificial multi-headed myosin motors capable of bidirectional movement.
• Utilized optogenetics for light-controlled, selective cargo transport (receptors, organelles, actin remodelers).
• Employed advanced in vivo imaging in axolotls to observe and modulate filopodial dynamics during regeneration.

Main Results:

• Demonstrated successful transport of various cargo types within filopodia and neurites.
• Showcased control over the dynamics of filopodia and neurites using the engineered motors.
• Observed that modulated filopodial extensions re-established Sonic Hedgehog signaling gradients during axolotl limb regeneration.

Conclusions:

• The developed optogenetic toolbox offers unprecedented control over cellular communication via actin-based extensions.
• This technology has significant potential for manipulating cellular dynamics and understanding regenerative processes.
• The findings highlight a new approach to study and engineer cell-cell signaling pathways.