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Status: Bibliographieeintrag

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Verfasst von:Major, Luke G. [VerfasserIn]   i
 Holle, Andrew W. [VerfasserIn]   i
 Young, Jennifer [VerfasserIn]   i
 Hepburn, Matt S. [VerfasserIn]   i
 Jeong, Kwanghee [VerfasserIn]   i
 Chin, Ian L. [VerfasserIn]   i
 Sanderson, Rowan W. [VerfasserIn]   i
 Jeong, Ji Hoon [VerfasserIn]   i
 Aman, Zachary M. [VerfasserIn]   i
 Kennedy, Brendan F. [VerfasserIn]   i
 Hwang, Yongsung [VerfasserIn]   i
 Han, Dong-Wook [VerfasserIn]   i
 Park, Hyun Woo [VerfasserIn]   i
 Guan, Kun-Liang [VerfasserIn]   i
 Spatz, Joachim P. [VerfasserIn]   i
 Choi, Yu Suk [VerfasserIn]   i
Titel:Volume adaptation controls stem cell mechanotransduction
Verf.angabe:Luke G. Major, Andrew W. Holle, Jennifer L. Young, Matt S. Hepburn, Kwanghee Jeong, Ian L. Chin, Rowan W. Sanderson, Ji Hoon Jeong, Zachary M. Aman, Brendan F. Kennedy, Yongsung Hwang, Dong-Wook Han, Hyun Woo Park, Kun-Liang Guan, Joachim P. Spatz, and Yu Suk Choi
E-Jahr:2019
Jahr:November 12, 2019
Umfang:11 S.
Fussnoten:Gesehen am 16.04.2020
Titel Quelle:Enthalten in: American Chemical SocietyACS applied materials & interfaces
Ort Quelle:Washington, DC : Soc., 2009
Jahr Quelle:2019
Band/Heft Quelle:11(2019), 49, Seite 45520-45530
ISSN Quelle:1944-8252
Abstract:Recent studies have found discordant mechanosensitive outcomes when comparing 2D and 3D, highlighting the need for tools to study mechanotransduction in 3D across a wide spectrum of stiffness. A gelatin methacryloyl (GelMA) hydrogel with a continuous stiffness gradient ranging from 5 to 38 kPa was developed to recapitulate physiological stiffness conditions. Adipose-derived stem cells (ASCs) were encapsulated in this hydrogel, and their morphological characteristics and expression of both mechanosensitive proteins (Lamin A, YAP, and MRTFa) and differentiation markers (PPARγ and RUNX2) were analyzed. Low-stiffness regions (∼8 kPa) permitted increased cellular and nuclear volume and enhanced mechanosensitive protein localization in the nucleus. This trend was reversed in high stiffness regions (∼30 kPa), where decreased cellular and nuclear volumes and reduced mechanosensitive protein nuclear localization were observed. Interestingly, cells in soft regions exhibited enhanced osteogenic RUNX2 expression, while those in stiff regions upregulated the adipogenic regulator PPARγ, suggesting that volume, not substrate stiffness, is sufficient to drive 3D stem cell differentiation. Inhibition of myosin II (Blebbistatin) and ROCK (Y-27632), both key drivers of actomyosin contractility, resulted in reduced cell volume, especially in low-stiffness regions, causing a decorrelation between volume expansion and mechanosensitive protein localization. Constitutively active and inactive forms of the canonical downstream mechanotransduction effector TAZ were stably transfected into ASCs. Activated TAZ resulted in higher cellular volume despite increasing stiffness and a consistent, stiffness-independent translocation of YAP and MRTFa into the nucleus. Thus, volume adaptation as a function of 3D matrix stiffness can control stem cell mechanotransduction and differentiation.
DOI:doi:10.1021/acsami.9b19770
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext ; Verlag: https://doi.org/10.1021/acsami.9b19770
 Volltext: https://pubs.acs.org/doi/10.1021/acsami.9b19770
 DOI: https://doi.org/10.1021/acsami.9b19770
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1694658171
Verknüpfungen:→ Zeitschrift

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