Programming Spatial Cell Sorting by Engineering Cadherin Intracellular Activity.
ACS Synth Biol
; 13(6): 1705-1715, 2024 Jun 21.
Article
in En
| MEDLINE
| ID: mdl-38726686
ABSTRACT
The spatial sorting of cells into appropriate tissue compartments is essential for embryogenesis and tissue development. Spatial cell sorting is controlled by the interplay between cell surface affinity and intracellular mechanical properties. However, intracellular signaling that can sufficiently sort cell populations remains unexplored. In this study, we engineered chimeric cadherins by replacing the cadherin intracellular domain with cytoskeletal regulators to test their ability to induce spatial cell sorting. Using a fibroblast-based reconstitution system, we observed that Rac1 and RhoA activity in the cadherin tail induced outward and inward sorting, respectively. In particular, RhoA activity embedded cells toward the inside of E-cadherin-expressing spheroids and tumor spheroids, leading to tissue invagination. Despite the simplicity of chimeric cadherin design, our results indicate that differences in cadherin intracellular activities can determine the direction of spatial cell sorting, even when cell surface affinity is not different, and provide new molecular tools to engineer tissue architectures.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cadherins
/
Rac1 GTP-Binding Protein
/
RhoA GTP-Binding Protein
Limits:
Animals
/
Humans
Language:
En
Journal:
ACS Synth Biol
/
ACS synth. biol
/
ACS synthetic biology
Year:
2024
Document type:
Article
Affiliation country:
Japón
Country of publication:
Estados Unidos