title: Dynamic phototuning of 3D hydrogel stiffness.
abstract: Hydrogels are widely used as in vitro culture models to mimic 3D cellular microenvironments. The stiffness of the extracellular matrix is known to influence cell phenotype, inspiring work toward unraveling the role of stiffness on cell behavior using hydrogels. However, in many biological processes such as embryonic development, wound healing, and tumorigenesis, the microenvironment is highly dynamic, leading to changes in matrix stiffness over a broad range of timescales. To recapitulate dynamic microenvironments, a hydrogel with temporally tunable stiffness is needed. Here, we present a system in which alginate gel stiffness can be temporally modulated by light-triggered release of calcium or a chelator from liposomes. Others have shown softening via photodegradation or stiffening via secondary cross-linking; however, our system is capable of both dynamic stiffening and softening. Dynamic modulation of stiffness can be induced at least 14 d after gelation and can be spatially controlled to produce gradients and patterns. We use this system to investigate the regulation of fibroblast morphology by stiffness in both nondegradable gels and gels with degradable elements. Interestingly, stiffening inhibits fibroblast spreading through either mesenchymal or amoeboid migration modes. We demonstrate this technology can be translated in vivo by using deeply penetrating near-infrared light for transdermal stiffness modulation, enabling external control of gel stiffness. Temporal modulation of hydrogel stiffness is a powerful tool that will enable investigation of the role that dynamic microenvironments play in biological processes both in vitro and in well-controlled in vivo experiments.
authors: Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712.
authors: Ryan S
authors: RS
authors: Stowers
authors: Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712.
authors: Shane C
authors: SC
authors: Allen
authors: Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712 suggs@utexas.edu.
authors: Laura J
authors: LJ
authors: Suggs
mesh_terms: D060833:Cellular Microenvironment; D020100:Hydrogels; D008954:Models, Biological
chemical_list: D020100:Hydrogels
keywords: cell spreading; dynamic microenvironment; hydrogel; transdermal
references: Nat Mater. 2010 Jun;9(6):518-26
references: 20418863
references: Soft Matter. 2014 Jun 28;10(24):4268-74
references: 24781036
references: Biomacromolecules. 2005 Jan-Feb;6(1):290-301
references: 15638532
references: Cell Motil Cytoskeleton. 2005 Jan;60(1):24-34
references: 15573414
references: J Cell Biol. 2010 Jan 11;188(1):11-9
references: 19951899
references: Nat Biotechnol. 2001 Apr;19(4):316-7
references: 11283581
references: Biophys J. 2000 Jul;79(1):144-52
references: 10866943
references: Biomaterials. 2012 Oct;33(29):6943-51
references: 22800539
references: Am J Physiol Heart Circ Physiol. 2006 Jun;290(6):H2196-203
references: 16473959
references: Biomaterials. 2011 Feb;32(4):1002-9
references: 21071078
references: Biomaterials. 2010 Nov;31(32):8228-34
references: 20674004
references: Nat Commun. 2012;3:792
references: 22531177
references: Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13661-5
references: 9391082
references: Biochim Biophys Acta. 1994 Nov 2;1195(2):237-44
references: 7947916
references: J Tissue Eng Regen Med. 2009 Feb;3(2):77-84
references: 19051218
references: Science. 2009 Apr 3;324(5923):59-63
references: 19342581
references: Biophys J. 2004 Jan;86(1 Pt 1):617-28
references: 14695306
references: Nat Mater. 2013 May;12(5):458-65
references: 23524375
references: J Cell Biol. 2010 Aug 23;190(4):693-706
references: 20733059
references: Nanotechnology. 2014 Jan 10;25(1):014004
references: 24334436
references: Biomaterials. 2005 Apr;26(11):1211-8
references: 15475050
references: Development. 1995 Oct;121(10):3131-40
references: 7588048
references: Am J Physiol Gastrointest Liver Physiol. 2007 Dec;293(6):G1147-54
references: 17932231
references: Cell. 2009 Nov 25;139(5):891-906
references: 19931152
references: Biomed Microdevices. 2010 Feb;12(1):145-51
references: 19830565
references: Cancer Cell. 2005 Sep;8(3):241-54
references: 16169468
references: Cell. 2006 Aug 25;126(4):677-89
references: 16923388
references: Biotechnol Bioeng. 2009 Jul 1;103(4):655-63
references: 19472329
references: Biomaterials. 2014 Oct;35(32):8927-36
references: 25047628
references: Nat Mater. 2012 Aug;11(8):734-41
references: 22751180
references: Adv Mater. 2009 Sep 4;21(32-33):3307-29
references: 20882499
references: Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5413-8
references: 12686696
references: Adv Mater. 2010 Feb 9;22(6):686-91
references: 20217770