Volume adaptation controls stem cell mechanotransduction

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 dev...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Major, Luke G. (VerfasserIn) , Holle, Andrew W. (VerfasserIn) , Young, Jennifer (VerfasserIn) , Hepburn, Matt S. (VerfasserIn) , Jeong, Kwanghee (VerfasserIn) , Chin, Ian L. (VerfasserIn) , Sanderson, Rowan W. (VerfasserIn) , Jeong, Ji Hoon (VerfasserIn) , Aman, Zachary M. (VerfasserIn) , Kennedy, Brendan F. (VerfasserIn) , Hwang, Yongsung (VerfasserIn) , Han, Dong-Wook (VerfasserIn) , Park, Hyun Woo (VerfasserIn) , Guan, Kun-Liang (VerfasserIn) , Spatz, Joachim P. (VerfasserIn) , Choi, Yu Suk (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: November 12, 2019
In: ACS applied materials & interfaces
Year: 2019, Jahrgang: 11, Heft: 49, Pages: 45520-45530
ISSN:1944-8252
DOI:10.1021/acsami.9b19770
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1021/acsami.9b19770
Verlag, lizenzpflichtig, Volltext: https://pubs.acs.org/doi/10.1021/acsami.9b19770
Volltext
Verfasserangaben: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

MARC

LEADER 00000caa a2200000 c 4500
001 1694658171
003 DE-627
005 20230427070515.0
007 cr uuu---uuuuu
008 200416s2019 xx |||||o 00| ||eng c
024 7 |a 10.1021/acsami.9b19770  |2 doi 
035 |a (DE-627)1694658171 
035 |a (DE-599)KXP1694658171 
035 |a (OCoLC)1341315197 
040 |a DE-627  |b ger  |c DE-627  |e rda 
041 |a eng 
084 |a 33  |2 sdnb 
100 1 |a Major, Luke G.  |e VerfasserIn  |0 (DE-588)1208405888  |0 (DE-627)1694658996  |4 aut 
245 1 0 |a Volume adaptation controls stem cell mechanotransduction  |c 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 
264 1 |c November 12, 2019 
300 |a 11 
336 |a Text  |b txt  |2 rdacontent 
337 |a Computermedien  |b c  |2 rdamedia 
338 |a Online-Ressource  |b cr  |2 rdacarrier 
500 |a Gesehen am 16.04.2020 
520 |a 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. 
700 1 |a Holle, Andrew W.  |e VerfasserIn  |0 (DE-588)1165158566  |0 (DE-627)1029325294  |0 (DE-576)510275540  |4 aut 
700 1 |a Young, Jennifer  |e VerfasserIn  |0 (DE-588)1165167476  |0 (DE-627)1029328587  |0 (DE-576)510279120  |4 aut 
700 1 |a Hepburn, Matt S.  |e VerfasserIn  |4 aut 
700 1 |a Jeong, Kwanghee  |e VerfasserIn  |4 aut 
700 1 |a Chin, Ian L.  |e VerfasserIn  |4 aut 
700 1 |a Sanderson, Rowan W.  |e VerfasserIn  |4 aut 
700 1 |a Jeong, Ji Hoon  |e VerfasserIn  |4 aut 
700 1 |a Aman, Zachary M.  |e VerfasserIn  |4 aut 
700 1 |a Kennedy, Brendan F.  |e VerfasserIn  |4 aut 
700 1 |a Hwang, Yongsung  |e VerfasserIn  |4 aut 
700 1 |a Han, Dong-Wook  |e VerfasserIn  |4 aut 
700 1 |a Park, Hyun Woo  |e VerfasserIn  |4 aut 
700 1 |a Guan, Kun-Liang  |e VerfasserIn  |4 aut 
700 1 |a Spatz, Joachim P.  |d 1969-  |e VerfasserIn  |0 (DE-588)122582675  |0 (DE-627)08203124X  |0 (DE-576)173014771  |4 aut 
700 1 |a Choi, Yu Suk  |e VerfasserIn  |4 aut 
773 0 8 |i Enthalten in  |a American Chemical Society  |t ACS applied materials & interfaces  |d Washington, DC : Soc., 2009  |g 11(2019), 49, Seite 45520-45530  |h Online-Ressource  |w (DE-627)587139617  |w (DE-600)2467494-1  |w (DE-576)299311139  |x 1944-8252  |7 nnas 
773 1 8 |g volume:11  |g year:2019  |g number:49  |g pages:45520-45530  |g extent:11  |a Volume adaptation controls stem cell mechanotransduction 
856 4 0 |u https://doi.org/10.1021/acsami.9b19770  |x Verlag  |x Resolving-System  |z lizenzpflichtig  |3 Volltext 
856 4 0 |u https://pubs.acs.org/doi/10.1021/acsami.9b19770  |x Verlag  |z lizenzpflichtig  |3 Volltext 
951 |a AR 
992 |a 20200416 
993 |a Article 
994 |a 2019 
998 |g 122582675  |a Spatz, Joachim P.  |m 122582675:Spatz, Joachim P.  |d 120000  |d 120300  |e 120000PS122582675  |e 120300PS122582675  |k 0/120000/  |k 1/120000/120300/  |p 15 
998 |g 1165167476  |a Young, Jennifer  |m 1165167476:Young, Jennifer  |p 3 
998 |g 1165158566  |a Holle, Andrew W.  |m 1165158566:Holle, Andrew W.  |p 2 
999 |a KXP-PPN1694658171  |e 3624012142 
BIB |a Y 
SER |a journal 
JSO |a {"person":[{"family":"Major","given":"Luke G.","roleDisplay":"VerfasserIn","display":"Major, Luke G.","role":"aut"},{"roleDisplay":"VerfasserIn","display":"Holle, Andrew W.","role":"aut","family":"Holle","given":"Andrew W."},{"given":"Jennifer","family":"Young","role":"aut","display":"Young, Jennifer","roleDisplay":"VerfasserIn"},{"family":"Hepburn","given":"Matt S.","roleDisplay":"VerfasserIn","display":"Hepburn, Matt S.","role":"aut"},{"roleDisplay":"VerfasserIn","display":"Jeong, Kwanghee","role":"aut","family":"Jeong","given":"Kwanghee"},{"display":"Chin, Ian L.","roleDisplay":"VerfasserIn","role":"aut","family":"Chin","given":"Ian L."},{"role":"aut","display":"Sanderson, Rowan W.","roleDisplay":"VerfasserIn","given":"Rowan W.","family":"Sanderson"},{"roleDisplay":"VerfasserIn","display":"Jeong, Ji Hoon","role":"aut","family":"Jeong","given":"Ji Hoon"},{"given":"Zachary M.","family":"Aman","role":"aut","display":"Aman, Zachary M.","roleDisplay":"VerfasserIn"},{"roleDisplay":"VerfasserIn","display":"Kennedy, Brendan F.","role":"aut","family":"Kennedy","given":"Brendan F."},{"family":"Hwang","given":"Yongsung","roleDisplay":"VerfasserIn","display":"Hwang, Yongsung","role":"aut"},{"role":"aut","roleDisplay":"VerfasserIn","display":"Han, Dong-Wook","given":"Dong-Wook","family":"Han"},{"role":"aut","roleDisplay":"VerfasserIn","display":"Park, Hyun Woo","given":"Hyun Woo","family":"Park"},{"given":"Kun-Liang","family":"Guan","role":"aut","display":"Guan, Kun-Liang","roleDisplay":"VerfasserIn"},{"roleDisplay":"VerfasserIn","display":"Spatz, Joachim P.","role":"aut","family":"Spatz","given":"Joachim P."},{"family":"Choi","given":"Yu Suk","roleDisplay":"VerfasserIn","display":"Choi, Yu Suk","role":"aut"}],"title":[{"title_sort":"Volume adaptation controls stem cell mechanotransduction","title":"Volume adaptation controls stem cell mechanotransduction"}],"note":["Gesehen am 16.04.2020"],"type":{"media":"Online-Ressource","bibl":"article-journal"},"language":["eng"],"recId":"1694658171","name":{"displayForm":["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"]},"origin":[{"dateIssuedKey":"2019","dateIssuedDisp":"November 12, 2019"}],"id":{"eki":["1694658171"],"doi":["10.1021/acsami.9b19770"]},"physDesc":[{"extent":"11 S."}],"relHost":[{"titleAlt":[{"title":"Applied materials & interfaces"}],"part":{"volume":"11","text":"11(2019), 49, Seite 45520-45530","extent":"11","year":"2019","issue":"49","pages":"45520-45530"},"pubHistory":["1.2009 -"],"recId":"587139617","corporate":[{"display":"American Chemical Society","roleDisplay":"VerfasserIn","role":"aut"}],"language":["eng"],"disp":"American Chemical SocietyACS applied materials & interfaces","note":["Gesehen am 27.08.2020"],"type":{"media":"Online-Ressource","bibl":"periodical"},"title":[{"title":"ACS applied materials & interfaces","title_sort":"ACS applied materials & interfaces"}],"physDesc":[{"extent":"Online-Ressource"}],"id":{"zdb":["2467494-1"],"eki":["587139617"],"issn":["1944-8252"]},"origin":[{"publisher":"Soc.","dateIssuedKey":"2009","dateIssuedDisp":"2009-","publisherPlace":"Washington, DC"}],"name":{"displayForm":["American Chemical Society"]}}]} 
SRT |a MAJORLUKEGVOLUMEADAP1220