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Programming Spatial Cell Sorting by Engineering Cadherin Intracellular Activity.

Authors :
Baba H
Fujita T
Mizuno K
Tambo M
Toda S
Source :
ACS synthetic biology [ACS Synth Biol] 2024 Jun 21; Vol. 13 (6), pp. 1705-1715. Date of Electronic Publication: 2024 May 10.
Publication Year :
2024

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.

Details

Language :
English
ISSN :
2161-5063
Volume :
13
Issue :
6
Database :
MEDLINE
Journal :
ACS synthetic biology
Publication Type :
Academic Journal
Accession number :
38726686
Full Text :
https://doi.org/10.1021/acssynbio.3c00774