The laminin-keratin link shields the nucleus from mechanical deformation and signalling.
Nat Mater
; 22(11): 1409-1420, 2023 Nov.
Article
em En
| MEDLINE
| ID: mdl-37709930
ABSTRACT
The mechanical properties of the extracellular matrix dictate tissue behaviour. In epithelial tissues, laminin is a very abundant extracellular matrix component and a key supporting element. Here we show that laminin hinders the mechanoresponses of breast epithelial cells by shielding the nucleus from mechanical deformation. Coating substrates with laminin-111-unlike fibronectin or collagen I-impairs cell response to substrate rigidity and YAP nuclear localization. Blocking the laminin-specific integrin ß4 increases nuclear YAP ratios in a rigidity-dependent manner without affecting the cell forces or focal adhesions. By combining mechanical perturbations and mathematical modelling, we show that ß4 integrins establish a mechanical linkage between the substrate and keratin cytoskeleton, which stiffens the network and shields the nucleus from actomyosin-mediated mechanical deformation. In turn, this affects the nuclear YAP mechanoresponses, chromatin methylation and cell invasion in three dimensions. Our results demonstrate a mechanism by which tissues can regulate their sensitivity to mechanical signals.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Laminina
/
Queratinas
Idioma:
En
Revista:
Nat Mater
Assunto da revista:
CIENCIA
/
QUIMICA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Espanha