Engineering Programmable Material-To-Cell Pathways Via Synthetic Notch Receptors To Spatially Control Cellular...

Area of Science:

• Synthetic biology
• Biomaterials engineering
• Cellular engineering

Background:

• Synthetic Notch (synNotch) receptors enable cells to respond to signals from neighbors by activating specific genetic programs.
• Current synNotch applications are limited by cell-presented ligands, restricting spatial control in tissue engineering.
• Developing material-based platforms is crucial for precise, user-defined material-to-cell signaling.

Approach:

• Conjugated synNotch ligands to extracellular matrix proteins (fibronectin) using genetic engineering.
• Utilized enzymatic and click chemistry to link ligands to gelatin hydrogels for cell activation.
• Employed microcontact printing and microfluidics to achieve microscale spatial patterning of ligands on surfaces.

Key Points:

• Demonstrated material-based activation of synNotch receptors for controlled cellular responses.
• Achieved precise spatial control over synNotch signaling using engineered materials.
• Successfully patterned tissues with multiple cell phenotypes by spatially presenting different synNotch ligands.

Conclusions:

• This work expands the synNotch toolkit with versatile material-based platforms.
• Provides novel methods for spatially controlling cellular phenotypes in mammalian systems.
• Offers broad applications in developmental biology, tissue modeling, and regenerative medicine.