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Engineering programmable material-to-cell pathways via synthetic notch receptors to spatially control differentiation
Mher Garibyan1,2,3, Tyler Hoffman4, Thijs Makaske1,2,5
1Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA.
Nature Communications
|July 13, 2024
Summary
Researchers developed new materials to control synthetic Notch (synNotch) receptors, enabling precise spatial control of cellular functions in tissue engineering applications.
Area of Science:
- Biomaterials Science
- Synthetic Biology
- Tissue Engineering
Background:
- Synthetic Notch (synNotch) receptors allow cells to sense signals and trigger specific genetic programs.
- Existing methods offer limited spatial control for synNotch ligands, especially on extracellular matrix (ECM) scaffolds crucial for tissue engineering.
Purpose of the Study:
- To create versatile materials for activating synNotch receptors, enabling precise control over material-to-cell signaling.
- To engineer tissues with microscale precision by controlling cellular phenotypes through engineered material-cell interactions.
Main Methods:
- Genetically and chemically conjugating synNotch ligands to ECM proteins and ECM-derived materials.
- Utilizing microcontact printing to pattern two orthogonal synNotch ligands on surfaces.
- Co-culturing cells with two synNotch programs to achieve four distinct reporter phenotypes with microscale precision.
Main Results:
- Successfully fused synNotch ligands to ECM components, creating novel signaling materials.
- Demonstrated microscale control over cellular phenotypes, generating four distinct reporter outputs.
- Showcased applications in tissue engineering by co-differentiating fibroblasts into specific cell types within defined micropatterns.
Conclusions:
- Developed a materials platform for generalizable engineering of material-to-cell signaling via synNotch receptors.
- Enabled precise spatial control of cellular phenotypes in mammalian tissues through engineered material-ligand interactions.
- Paved the way for advanced applications in regenerative medicine and synthetic biology.
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