title: Introduction to cell-hydrogel mechanosensing.
abstract: The development of hydrogel-based biomaterials represents a promising approach to generating new strategies for tissue engineering and regenerative medicine. In order to develop more sophisticated cell-seeded hydrogel constructs, it is important to understand how cells mechanically interact with hydrogels. In this paper, we review the mechanisms by which cells remodel hydrogels, the influence that the hydrogel mechanical and structural properties have on cell behaviour and the role of mechanical stimulation in cell-seeded hydrogels. Cell-mediated remodelling of hydrogels is directed by several cellular processes, including adhesion, migration, contraction, degradation and extracellular matrix deposition. Variations in hydrogel stiffness, density, composition, orientation and viscoelastic characteristics all affect cell activity and phenotype. The application of mechanical force on cells encapsulated in hydrogels can also instigate changes in cell behaviour. By improving our understanding of cell-material mechano-interactions in hydrogels, this should enable a new generation of regenerative medical therapies to be developed.
authors.affiliation: Trinity Centre for Bioengineering , Trinity Biomedical Sciences Institute, Trinity College Dublin , Dublin 2 , Ireland ; Department of Mechanical and Manufacturing Engineering, School of Engineering , Trinity College Dublin , Dublin , Ireland.
authors.forename: Mark
authors.initials: M
authors.lastname: Ahearne
keywords: adhesion; bioreactor; contraction; hydrogel; mechanobiology; tissue engineering
references.citation: Cell. 1992 Apr 3;69(1):11-25
references.pmid: 1555235
references.citation: J Mech Behav Biomed Mater. 2008 Jan;1(1):59-67
references.pmid: 19627772
references.citation: J Dent Res. 2001 Nov;80(11):2025-9
references.pmid: 11759015
references.citation: J Tissue Eng Regen Med. 2009 Feb;3(2):77-84
references.pmid: 19051218
references.citation: Biomaterials. 2013 Jul;34(21):5070-7
references.pmid: 23587444
references.citation: J Control Release. 2012 Dec 28;164(3):291-8
references.pmid: 22776290
references.citation: Science. 2005 Nov 18;310(5751):1139-43
references.pmid: 16293750
references.citation: Prog Clin Biol Res. 1987;249:251-62
references.pmid: 3671428
references.citation: Tissue Eng Part A. 2010 Oct;16(10):3099-109
references.pmid: 20586613
references.citation: Science. 2001 Nov 23;294(5547):1708-12
references.pmid: 11721053
references.citation: Annu Rev Cell Dev Biol. 2010;26:421-44
references.pmid: 20507227
references.citation: Biomaterials. 1999 Jan;20(1):45-53
references.pmid: 9916770
references.citation: Nat Mater. 2004 Apr;3(4):249-53
references.pmid: 15034559
references.citation: Biophys J. 2007 Apr 15;92(8):2964-74
references.pmid: 17277192
references.citation: J Cell Biol. 2006 Jan 2;172(1):41-53
references.pmid: 16380439
references.citation: Acta Biomater. 2005 Nov;1(6):625-33
references.pmid: 16701843
references.citation: Cell. 2006 Aug 25;126(4):645-7
references.pmid: 16923382
references.citation: Acta Biomater. 2010 Sep;6(9):3404-14
references.pmid: 20385260
references.citation: Nature. 2008 May 15;453(7193):338-44
references.pmid: 18480815
references.citation: J Artif Organs. 2012 Sep;15(3):215-24
references.pmid: 22527978
references.citation: Methods Mol Med. 1999;18:67-73
references.pmid: 21370168
references.citation: J Mech Behav Biomed Mater. 2011 Oct;4(7):1257-65
references.pmid: 21783134
references.citation: Invest Ophthalmol Vis Sci. 2006 Aug;47(8):3311-7
references.pmid: 16877396
references.citation: Sci Rep. 2012;2:488
references.pmid: 22761994
references.citation: Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15346-51
references.pmid: 14660789
references.citation: Nat Mater. 2008 Aug;7(8):636-40
references.pmid: 18511938
references.citation: Biomaterials. 2001 Mar;22(6):511-21
references.pmid: 11219714
references.citation: Acta Biomater. 2011 Oct;7(10):3719-28
references.pmid: 21704737
references.citation: Science. 2001 May 25;292(5521):1502-6
references.pmid: 11379633
references.citation: Biomaterials. 2011 Sep;32(27):6425-34
references.pmid: 21652067
references.citation: Ann Biomed Eng. 2000 Jan;28(1):110-8
references.pmid: 10645794
references.citation: J R Soc Interface. 2010 Dec 6;7 Suppl 6:S707-16
references.pmid: 20926429
references.citation: Graefes Arch Clin Exp Ophthalmol. 2009 Nov;247(11):1477-86
references.pmid: 19590887
references.citation: Tissue Eng Part A. 2010 Jun;16(6):2091-100
references.pmid: 20109018
references.citation: Biotechnol Lett. 2005 Mar;27(5):317-22
references.pmid: 15834792
references.citation: Biotechnol Lett. 2006 Sep;28(18):1415-23
references.pmid: 16955350
references.citation: Biotechnol Bioeng. 2010 Apr 15;105(6):1148-60
references.pmid: 20014437
references.citation: J Tissue Eng Regen Med. 2009 Oct;3(7):493-500
references.pmid: 19598145
references.citation: Tissue Eng Part A. 2012 Sep;18(17-18):1837-48
references.pmid: 22519549
references.citation: Nanotechnology. 2012 Mar 9;23(9):095705
references.pmid: 22322583
references.citation: Biomaterials. 2009 Sep;30(27):4695-9
references.pmid: 19539367
references.citation: Biochem Cell Biol. 1995 Jul-Aug;73(7-8):391-7
references.pmid: 8703411
references.citation: J R Soc Interface. 2005 Dec 22;2(5):455-63
references.pmid: 16849205
references.citation: Biotechnol Bioeng. 2003 Jun 5;82(5):578-89
references.pmid: 12652481
references.citation: J Tissue Eng Regen Med. 2008 Dec;2(8):521-4
references.pmid: 18956413
references.citation: Biomaterials. 2006 Mar;27(8):1579-85
references.pmid: 16140372
references.citation: ACS Nano. 2012 Jan 24;6(1):362-72
references.pmid: 22117858
references.citation: Biomaterials. 2012 May;33(15):3852-9
references.pmid: 22401852
references.citation: J Appl Biomater. 1991 Summer;2(2):101-7
references.pmid: 10171121
references.citation: Tissue Eng Part A. 2010 Oct;16(10):3173-84
references.pmid: 20649441
references.citation: Eur Cell Mater. 2013 Feb 07;25:167-78
references.pmid: 23389751
references.citation: Structure. 2001 Nov;9(11):1061-9
references.pmid: 11709170
references.citation: Biomaterials. 2007 Jun;28(17):2706-17
references.pmid: 17346788
references.citation: Adv Drug Deliv Rev. 2007 Nov 10;59(13):1299-305
references.pmid: 17825456
references.citation: Biomaterials. 2012 Oct;33(29):6943-51
references.pmid: 22800539
references.citation: Biomaterials. 2010 May;31(13):3596-603
references.pmid: 20153045
references.citation: J R Soc Interface. 2009 May 6;6(34):471-8
references.pmid: 18753124
references.citation: Cell. 1987 Feb 27;48(4):549-54
references.pmid: 3028640
references.citation: Biochem J. 1984 May 1;219(3):1057-9
references.pmid: 6743242
references.citation: J Biomater Sci Polym Ed. 2012;23(16):2025-38
references.pmid: 22023724
references.citation: Biomaterials. 2002 Jul;23(13):2717-22
references.pmid: 12059021
references.citation: Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6728-33
references.pmid: 10841570
references.citation: Biomed Microdevices. 2010 Aug;12(4):627-35
references.pmid: 20300856
references.citation: J R Soc Interface. 2010 Oct 6;7 Suppl 5:S649-61
references.pmid: 20671067
references.citation: Biomaterials. 2010 Oct;31(30):7836-45
references.pmid: 20667588
references.citation: Biopolymers. 2012 Mar;97(3):177-88
references.pmid: 21994046
references.citation: J Biomed Mater Res A. 2006 Jun 15;77(4):688-99
references.pmid: 16514602
references.citation: Development. 2013 Jan 15;140(2):255-65
references.pmid: 23250203
references.citation: Biomaterials. 2000 Dec;21(24):2529-43
references.pmid: 11071603
references.citation: Exp Eye Res. 2010 Nov;91(5):584-91
references.pmid: 20678499
references.citation: Biophys J. 2000 Jul;79(1):144-52
references.pmid: 10866943
references.citation: J Cell Physiol. 2005 Jul;204(1):198-209
references.pmid: 15669099
references.citation: Biorheology. 2009;46(5):417-37
references.pmid: 19940357
references.citation: J Mater Sci Mater Med. 2010 Oct;21(10):2869-79
references.pmid: 20717710
references.citation: J Biomed Mater Res. 1973 Nov;7(6):509-22
references.pmid: 4589048
references.citation: J Biomed Mater Res B Appl Biomater. 2004 Oct 15;71(1):181-7
references.pmid: 15368243
references.citation: J Mater Sci Mater Med. 2010 Sep;21(9):2593-600
references.pmid: 20577785
references.citation: Biomech Model Mechanobiol. 2012 May;11(5):689-702
references.pmid: 21853351
references.citation: Soft Matter. 2012 Oct 21;8(39):10141-10148
references.pmid: 23226161
references.citation: FASEB J. 2011 May;25(5):1486-96
references.pmid: 21282205
references.citation: J Hand Surg Br. 2003 Oct;28(5):465-70
references.pmid: 12954258
references.citation: J Biomed Mater Res. 2002 Mar 5;59(3):429-37
references.pmid: 11774300
references.citation: J Biomech. 2006;39(6):1136-44
references.pmid: 16256125
references.citation: J Biomech Eng. 2000 Jun;122(3):252-60
references.pmid: 10923293
references.citation: Biomaterials. 2010 May;31(13):3736-43
references.pmid: 20138664
references.citation: J R Soc Interface. 2011 Jul 6;8(60):998-1010
references.pmid: 21247946
references.citation: Biomaterials. 1999 Jun;20(12):1143-50
references.pmid: 10382830
references.citation: Nanomedicine. 2011 Apr;7(2):131-6
references.pmid: 21272664
references.citation: Tissue Eng Part A. 2010 Nov;16(11):3457-66
references.pmid: 20666585
references.citation: J Tissue Eng Regen Med. 2016 Jan;10(1):81-91
references.pmid: 23229842
references.citation: Biotechnol Bioeng. 1996 May 20;50(4):357-64
references.pmid: 18626984
references.citation: Biomaterials. 2000 Dec;21(24):2589-98
references.pmid: 11071608
references.citation: Cell. 2005 Dec 2;123(5):769-72
references.pmid: 16325573
references.citation: J Mech Behav Biomed Mater. 2012 Jul;11:82-91
references.pmid: 22658157
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12285-90
references.pmid: 16895989
references.citation: Acta Biomater. 2012 Jul;8(6):2153-9
references.pmid: 22426136
references.citation: Biomaterials. 2012 Apr;33(11):3093-106
references.pmid: 22265788
references.citation: Tissue Eng Part B Rev. 2008 Jun;14(2):199-215
references.pmid: 18544016
references.citation: Biotechnol J. 2009 May;4(5):730-7
references.pmid: 19452469
references.citation: Acta Biomater. 2008 Jul;4(4):967-75
references.pmid: 18359671
references.citation: Tissue Eng Part A. 2011 Apr;17(7-8):1111-22
references.pmid: 21142626
references.citation: Br J Ophthalmol. 2008 Feb;92(2):268-71
references.pmid: 18055575
references.citation: FASEB J. 2002 May;16(7):751-3
references.pmid: 11923220
references.citation: Tissue Eng. 2002 Dec;8(6):931-9
references.pmid: 12542939
references.citation: Ann N Y Acad Sci. 2004 May;1015:299-311
references.pmid: 15201169
references.citation: Biotechnol Appl Biochem. 2011 Sep-Oct;58(5):345-52
references.pmid: 21995537
references.citation: Biomech Model Mechanobiol. 2007 Jan;6(1-2):113-25
references.pmid: 16691412
references.citation: Cell. 2006 Aug 25;126(4):677-89
references.pmid: 16923388
references.citation: Nanoscale Res Lett. 2011 Apr 07;6(1):312
references.pmid: 21711840
references.citation: Proc Natl Acad Sci U S A. 1979 Mar;76(3):1274-8
references.pmid: 286310
references.citation: Biomaterials. 2005 May;26(14):2001-12
references.pmid: 15576174
references.citation: Am J Physiol Heart Circ Physiol. 2007 Jan;292(1):H28-42
references.pmid: 16951049
references.citation: J R Soc Interface. 2007 Dec 22;4(17):1169-73
references.pmid: 17472904
references.citation: J Biosci Bioeng. 2005 Sep;100(3):235-45
references.pmid: 16243271
references.citation: Biomaterials. 2011 Jan;32(1):107-18
references.pmid: 20880579
references.citation: Tissue Eng Part B Rev. 2010 Dec;16(6):577-85
references.pmid: 20735319
references.citation: Tissue Eng Part C Methods. 2010 Apr;16(2):319-27
references.pmid: 19563255
references.citation: J Cell Physiol. 1999 Feb;178(2):197-204
references.pmid: 10048584
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5413-8
references.pmid: 12686696
references.citation: J Mater Sci Mater Med. 2010 Apr;21(4):1163-8
references.pmid: 20052519
references.citation: Adv Healthc Mater. 2013 Jul;2(7):945-51
references.pmid: 23335423
references.citation: J Am Chem Soc. 2011 Feb 16;133(6):1686-9
references.pmid: 21247159
references.citation: Cell. 2002 Sep 20;110(6):673-87
references.pmid: 12297042
references.citation: Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):20976-81
references.pmid: 22171002
references.citation: Biomed Mater. 2013 Jun;8(3):035004
references.pmid: 23532058
references.citation: Adv Drug Deliv Rev. 2009 Oct 5;61(12):1097-114
references.pmid: 19647768
references.citation: Biomaterials. 2010 Oct;31(30):7726-37
references.pmid: 20674002
references.citation: Lab Chip. 2007 Jun;7(6):763-9
references.pmid: 17538719
references.citation: Biotechnol J. 2013 Apr;8(4):472-84
references.pmid: 23390141
references.citation: Dev Cell. 2006 Jan;10(1):11-20
references.pmid: 16399074
references.citation: Biomacromolecules. 2011 May 9;12(5):1641-50
references.pmid: 21413708
references.citation: PLoS One. 2013 Apr 09;8(4):e60728
references.pmid: 23593296
references.citation: J Cell Sci. 1994 Nov;107 ( Pt 11):3037-44
references.pmid: 7699003
references.citation: Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9996-10001
references.pmid: 12119393
references.citation: J Biomed Mater Res. 2000 Jun 15;50(4):518-27
references.pmid: 10756310
references.citation: Am J Physiol Cell Physiol. 2007 May;292(5):C1830-6
references.pmid: 17251324
references.citation: Tissue Eng Part B Rev. 2009 Mar;15(1):43-53
references.pmid: 19196119
references.citation: Cytotherapy. 2005;7(5):447-55
references.pmid: 16236634
references.citation: J Periodontal Res. 2011 Aug;46(4):448-55
references.pmid: 21488874
references.citation: Science. 1993 May 14;260(5110):920-6
references.pmid: 8493529
references.citation: J Biomed Mater Res. 2002 Jun 15;60(4):613-21
references.pmid: 11948520
references.citation: Biomacromolecules. 2007 Feb;8(2):406-15
references.pmid: 17253761
references.citation: Biomaterials. 2013 Jan;34(4):940-51
references.pmid: 23141898
references.citation: FEBS Lett. 1989 Jul 3;250(2):301-5
references.pmid: 2546801
references.citation: Connect Tissue Res. 2013;54(3):159-66
references.pmid: 23323769
references.citation: Stem Cells Transl Med. 2013 Apr;2(4):297-306
references.pmid: 23486832
references.citation: Biomaterials. 2010 Nov;31(32):8454-64
references.pmid: 20684983
references.citation: J Biol Chem. 1995 Mar 17;270(11):5872-6
references.pmid: 7890717
references.citation: Eur Cell Mater. 2012 Jan 29;23:28-40
references.pmid: 22287112
references.citation: Biomaterials. 2005 Oct;26(30):5991-8
references.pmid: 15878198
references.citation: J Cell Physiol. 1998 Jun;175(3):323-32
references.pmid: 9572477
references.citation: Biomaterials. 2009 Jan;30(2):196-207
references.pmid: 18922573
references.citation: Biomaterials. 1995 Dec;16(18):1385-93
references.pmid: 8590765
references.citation: Biophys Chem. 2003;100(1-3):593-605
references.pmid: 12646393
references.citation: Science. 1987 Oct 23;238(4826):491-7
references.pmid: 2821619
references.citation: Macromol Biosci. 2012 Aug;12(8):1077-89
references.pmid: 22648976
references.citation: Biomaterials. 2002 Nov;23(22):4315-23
references.pmid: 12219821
references.citation: Cell. 2012 May 25;149(5):1035-47
references.pmid: 22632968
references.citation: Nat Mater. 2013 May;12(5):458-65
references.pmid: 23524375
references.citation: Biomaterials. 2010 Jun;31(17):4639-56
references.pmid: 20303169
references.citation: Nat Rev Mol Cell Biol. 2007 Dec;8(12):957-69
references.pmid: 17971838
references.citation: Biophys J. 2008 Nov 1;95(9):4426-38
references.pmid: 18658232
references.citation: Exp Eye Res. 2013 Mar;108:42-7
references.pmid: 23287438
references.citation: Tissue Eng Part A. 2013 Nov;19(21-22):2439-51
references.pmid: 23815150
references.citation: Tissue Eng Part A. 2013 Jan;19(1-2):299-306
references.pmid: 22871265
references.citation: Biomacromolecules. 2011 Oct 10;12(10):3789-96
references.pmid: 21853977
references.citation: J Biol Chem. 2010 Jul 16;285(29):22276-81
references.pmid: 20463013
references.citation: Biomaterials. 2003 Sep;24(20):3475-81
references.pmid: 12809776
references.citation: J Mech Behav Biomed Mater. 2013 May;21:185-94
references.pmid: 23566770
references.citation: Chem Rev. 2001 Jul;101(7):1869-79
references.pmid: 11710233
references.citation: Int J Biochem Cell Biol. 2003 Jan;35(1):39-50
references.pmid: 12467646
references.citation: Nat Cell Biol. 2005 Feb;7(2):157-64
references.pmid: 15654332
references.citation: Science. 1994 Oct 7;266(5182):75-81
references.pmid: 7695699
references.citation: Acta Biomater. 2007 Jan;3(1):23-31
references.pmid: 16956800
references.citation: Nat Mater. 2012 May 27;11(7):642-9
references.pmid: 22635042
references.citation: J R Soc Interface. 2007 Dec 22;4(17):999-1030
references.pmid: 17412675
references.citation: Proc Natl Acad Sci U S A. 2006 Jul 18;103(29):10889-94
references.pmid: 16832052
references.citation: Stem Cell Res. 2012 May;8(3):403-9
references.pmid: 22386779
references.citation: Trends Biotechnol. 2004 Feb;22(2):80-6
references.pmid: 14757042
references.citation: Nature. 2008 Feb 7;451(7179):716-9
references.pmid: 18204438
references.citation: Tissue Eng Part B Rev. 2008 Jun;14(2):149-65
references.pmid: 18498217
references.citation: J Control Release. 2002 Sep 18;83(1):53-63
references.pmid: 12220838
references.citation: Arthritis Rheum. 2003 Oct;48(10):2865-72
references.pmid: 14558092
references.citation: Nat Rev Mol Cell Biol. 2008 Jun;9(6):446-54
references.pmid: 18464790
references.citation: Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3334-8
references.pmid: 7682699
references.citation: Cell Motil Cytoskeleton. 2009 Mar;66(3):121-8
references.pmid: 19170223
references.citation: Biorheology. 2003;40(1-3):79-85
references.pmid: 12454390
references.citation: J R Soc Interface. 2009 Jan 6;6(30):1-10
references.pmid: 18801715
references.citation: Chem Soc Rev. 2013 Sep 7;42(17):7335-72
references.pmid: 23609001
references.citation: J Biomech. 2010 Mar 22;43(5):920-6
references.pmid: 20005518