Synergistic effects of tethered growth factors and adhesion ligands on DNA synthesis and function of primary hepatocytes cultured on soft synthetic hydrogels

被引：40

作者：

Mehta, Geeta ^{[1
]}

Williams, Courtney M. ^{[1
]}

Alvarez, Luis ^{[1
]}

Lesniewski, Martha ^{[2
]}

Kamm, Roger D. ^{[1
,3
]}

Griffith, Linda G. ^{[1
,3
,4
,5
]}

机构：

[1] MIT, Dept Biol Engn, Cambridge, MA 02139 USA

[2] Georgia Inst Technol, Dept Mat Sci & Engn, Atlanta, GA 30332 USA

[3] MIT, Dept Mech Engn, Cambridge, MA 02139 USA

[4] MIT, Ctr Gynepathol Res, Cambridge, MA 02139 USA

[5] MIT, Ctr Environm Hlth Sci, Cambridge, MA 02139 USA

来源：

BIOMATERIALS | 2010年 / 31卷 / 17期

基金：

美国国家科学基金会;

关键词：

Self assembled peptide gel; Extracellular matrix; RGD cell binding domain; Heparin binding domain; Tethered growth factor; EXTRACELLULAR-MATRIX; RAT HEPATOCYTES; IN-VITRO; EGF RECEPTOR; TENASCIN-C; CELL; PEPTIDE; LIVER; EXPRESSION; KINASE;

D O I：

10.1016/j.biomaterials.2010.01.138

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

The composition, presentation, and spatial orientation of extracellular matrix molecules and growth factors are key regulators of cell behavior Here, we used self-assembling peptide nanofiber gels as a modular scaffold to investigate how fibronectin-derived adhesion ligands and different modes of epidermal growth factor (EGF) presentation synergistically regulate multiple facets of primary rat hepatocyte behavior in the context of a soft gel. In the presence of soluble EGF, inclusion of dimeric RGD and the heparin binding domain from fibronectin (HB) increased hepatocyte aggregation, spreading, and metabolic function compared to unmodified gels or gels modified with a single motif, but unlike rigid substrates, gels failed to induce DNA synthesis. Tethered EGF dramatically stimulated cell aggregation and spreading under all adhesive ligand conditions and also preserved metabolic function. Surprisingly, tethered EGF elicited DNA synthesis on gels with RGD and HB. Phenotypic differences between soluble and tethered EGF stimulation of cells on peptide gels are correlated with differences in expression and phosphorylation the EGF receptor and its heterodimerization partner ErbB2, and activation of the downstream signaling node ERK1/2 These modular matrices reveal new facets of hepatocellular biology in culture and may be more broadly useful in culture of other soft tissues. (C) 2010 Elsevier Ltd All rights reserved

引用

页码：4657 / 4671

页数：15

共 59 条

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