Soluble and multivalent Jag1 DNA origami nanopatterns activate Notch without pulling force

Area of Science:

• Cellular signaling pathways
• Developmental biology
• Neuroscience

Background:

• The Notch signaling pathway is crucial for embryonic development and nervous system function.
• Current models propose receptor activation relies on force-induced conformational changes.

Purpose of the Study:

• To investigate Notch signaling activation independent of pulling forces.
• To explore alternative mechanisms of Notch activation using soluble multivalent constructs.

Main Methods:

• Utilized DNA origami to create precise ligand nanopatterns displayed from solution.
• Treated neuroepithelial stem-like cells with these nanopatterns, including Jag1 clusters and chimeric structures.
• Analyzed Notch signaling activation under these conditions.

Main Results:

• Demonstrated Notch signaling activation without requiring pulling forces.
• Identified prolonged binding as a key factor in activation, even with modified ligand structures.
• Ruled out several potential confounding factors in the experimental setup.

Conclusions:

• Proposed a novel model for Notch activation involving prolonged ligand binding, independent of mechanical force.
• Established conditions for force-independent Notch activation, challenging existing paradigms.
• Laid the groundwork for developing novel soluble Notch agonists.