cell mechanics Dotaz Zobrazit nápovědu

6 228 záznamů v Medvik

Kniha

White cell mechanics : basic science and clinical aspects : proceedings of a symposium held at the Kroc Foundation, Santa Ynez Valley, May 2-6, 1983

New York : Alan R. Liss, 1984

Kroc Foundation series ; Vol. 16

318 s. : obr., tab., přeruš.bibliogr.

Článek

YAP regulates cell mechanics by controlling focal adhesion assembly

Here we unveil the molecular mechanism by which cell spreading and RhoA GTPase activity control FA formation ...

Nature communications. 2017 ; 8 (-) : 15321. [pub] 20170515

Nat Commun
ISSN 2041-1723
Medvik
Zdroj

Hippo effectors YAP/TAZ act as on-off mechanosensing switches by sensing modifications in extracellular matrix (ECM) composition and mechanics. The regulation of their activity has been described by a hierarchical model in which elements of Hippo pathway are under the control of focal adhesions (FAs). Here we unveil the molecular mechanism by which cell spreading and RhoA GTPase activity control FA formation through YAP to stabilize the anchorage of the actin cytoskeleton to the cell membrane. This mechanism requires YAP co-transcriptional function and involves the activation of genes encoding for integrins and FA docking proteins. Tuning YAP transcriptional activity leads to the modification of cell mechanics, force development and adhesion strength, and determines cell shape, migration and differentiation. These results provide new insights into the mechanism of YAP mechanosensing activity and qualify this Hippo effector as the key determinant of cell mechanics in response to ECM cues.

Článek

Substrate mechanics controls adipogenesis through YAP phosphorylation by dictating cell spreading

mechanoregulated proteins YAP/TAZ are involved in the adipogenic/osteogenic switch of mesenchymal stem cells ...

Biomaterials. 2019 ; 205 (-) : 64-80. [pub] 20190316

ISSN 1878-5905
Medvik
Zdroj

The mechanoregulated proteins YAP/TAZ are involved in the adipogenic/osteogenic switch of mesenchymal stem cells (MSCs). MSC fate decision can be unbalanced by controlling substrate mechanics, in turn altering the transmission of tension through cell cytoskeleton. MSCs have been proposed for orthopedic and reconstructive surgery applications. Thus, a tight control of their adipogenic potential is required in order to avoid their drifting towards fat tissue. Substrate mechanics has been shown to drive MSC commitment and to regulate YAP/TAZ protein shuttling and turnover. The mechanism by which YAP/TAZ co-transcriptional activity is mechanically regulated during MSC fate acquisition is still debated. Here, we design few bioengineering tools suited to disentangle the contribution of mechanical from biological stimuli to MSC adipogenesis. We demonstrate that the mechanical repression of YAP happens through its phosphorylation, is purely mediated by cell spreading downstream of substrate mechanics as dictated by dimensionality. YAP repression is sufficient to prompt MSC adipogenesis, regardless of a permissive biological environment, TEAD nuclear presence or focal adhesion stabilization. Finally, by harnessing the potential of YAP mechanical regulation, we propose a practical example of the exploitation of adipogenic transdifferentiation in tumors.