Programming Spatial Cell Sorting by Engineering Cadherin Intracellular Activity.
ACS Synth Biol
; 13(6): 1705-1715, 2024 Jun 21.
Article
em 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.
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Base de dados:
MEDLINE
Assunto principal:
Caderinas
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Proteínas rac1 de Ligação ao GTP
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Proteína rhoA de Ligação ao GTP
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article