Identification of matrix physicochemical properties required for renal epithelial cell tubulogenesis by using synthetic hydrogels.
J Cell Sci
; 132(20)2019 10 21.
Article
em En
| MEDLINE
| ID: mdl-31558679
ABSTRACT
Synthetic hydrogels with controlled physicochemical matrix properties serve as powerful in vitro tools to dissect cell-extracellular matrix (ECM) interactions that regulate epithelial morphogenesis in 3D microenvironments. In addition, these fully defined matrices overcome the lot-to-lot variability of naturally derived materials and have provided insights into the formation of rudimentary epithelial organs. Therefore, we engineered a fully defined synthetic hydrogel with independent control over proteolytic degradation, mechanical properties, and adhesive ligand type and density to study the impact of ECM properties on epithelial tubulogenesis for inner medullary collecting duct (IMCD) cells. Protease sensitivity of the synthetic material for membrane-type matrix metalloproteinase-1 (MT1-MMP, also known as MMP14) was required for tubulogenesis. Additionally, a defined range of matrix elasticity and presentation of RGD adhesive peptide at a threshold level of 2â
mM ligand density were required for epithelial tubulogenesis. Finally, we demonstrated that the engineered hydrogel supported organization of epithelial tubules with a lumen and secreted laminin. This synthetic hydrogel serves as a platform that supports epithelial tubular morphogenetic programs and can be tuned to identify ECM biophysical and biochemical properties required for epithelial tubulogenesis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hidrogéis
/
Células Epiteliais
/
Matriz Extracelular
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Microambiente Celular
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Túbulos Renais
/
Túbulos Renais Coletores
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Cell Sci
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos