DOI: 10.1098/rstb.2007.2114. Extracellular matrix, mechanotransduction and structural hierarchies in heart tissue engineering

Extracellular matrix, mechanotransduction and structural hierarchies in heart tissue engineering

10.1098/rstb.2007.2114

Crossref journal-article

The Royal Society

Philosophical Transactions of the Royal Society B: Biological Sciences (175)

Abstract

The spatial and temporal scales of cardiac organogenesis and pathogenesis make engineering of artificial heart tissue a daunting challenge. The temporal scales range from nanosecond conformational changes responsible for ion channel opening to fibrillation which occurs over seconds and can lead to death. Spatial scales range from nanometre pore sizes in membrane channels and gap junctions to the metre length scale of the whole cardiovascular system in a living patient. Synchrony over these scales requires a hierarchy of control mechanisms that are governed by a single common principle: integration of structure and function. To ensure that the function of ion channels and contraction of muscle cells lead to changes in heart chamber volume, an elegant choreography of metabolic, electrical and mechanical events are executed by protein networks composed of extracellular matrix, transmembrane integrin receptors and cytoskeleton which are functionally connected across all size scales. These structural control networks are mechanoresponsive, and they process mechanical and chemical signals in a massively parallel fashion, while also serving as a bidirectional circuit for information flow. This review explores how these hierarchical structural networks regulate the form and function of living cells and tissues, as well as how microfabrication techniques can be used to probe this structural control mechanism that maintains metabolic supply, electrical activation and mechanical pumping of heart muscle. Through this process, we delineate various design principles that may be useful for engineering artificial heart tissue in the future.

Bibliography

Parker, K. K., & Ingber, D. E. (2007). Extracellular matrix, mechanotransduction and structural hierarchies in heart tissue engineering. Philosophical Transactions of the Royal Society B: Biological Sciences, 362(1484), 1267â1279.

Authors 2

Kevin K Parker (first)
Donald E Ingber (additional)

References 96 Referenced 160

10.1016/S0344-0338(81)80120-3
10.1126/stke.2002.119.pe6 / Sci. STKE / Mechanotransduction: all signals point to cytoskeleton, matrix, and integrins by Alenghat F.J (2002)
10.1532/hsf.917
10.1152/ajpheart.00233.2002
10.3109/15419069809010789
10.1006/jmcc.1997.0465
{'key': 'e_1_3_2_8_1', 'first-page': '49', 'article-title': 'Structural basis of ventricular stiffness', 'volume': '44', 'author': 'Borg T.K', 'year': '1981', 'journal-title': 'Lab. Invest'} / Lab. Invest / Structural basis of ventricular stiffness by Borg T.K (1981)
10.1074/jbc.274.41.29282
10.1038/nm805
10.1242/jcs.37.1.391 / J. Cell Sci / Mechanical tension produced by nerve cells in tissue culture by Bray D (1979)
10.1021/la026394k
10.1085/jgp.200308899
10.1085/jgp.200409040
10.1161/01.RES.0000047530.88338.EB
10.1103/PhysRevE.64.041902
10.1016/j.cardiores.2004.08.020
10.1002/ar.1092360311
{'key': 'e_1_3_2_19_1', 'first-page': '364', 'article-title': 'The collagen network of the heart', 'volume': '40', 'author': 'Caulfield J.B', 'year': '1979', 'journal-title': 'Lab. Invest'} / Lab. Invest / The collagen network of the heart by Caulfield J.B (1979)
10.1126/science.276.5317.1425
{'key': 'e_1_3_2_21_1', 'first-page': '209', 'article-title': 'Using self-assembled monolayers to pattern ECM proteins and cells on substrates', 'volume': '139', 'author': 'Chen C.S', 'year': '2000', 'journal-title': 'Methods Mol. Biol'} / Methods Mol. Biol / Using self-assembled monolayers to pattern ECM proteins and cells on substrates by Chen C.S (2000)
10.1016/j.yjmcc.2004.03.006
10.1016/S0960-9822(06)00343-5
10.1073/pnas.94.17.9493
10.1007/s11626-999-0050-4
10.1083/jcb.99.6.2268
10.1242/jcs.112.10.1529 / J. Cell Sci / Myofibrillogenesis in the developing chicken heart: assembly of Z-disk, M-line and the thick filaments by Ehler E (1999)
10.1006/excr.1996.3451
10.1016/0026-2862(86)90052-X
10.1063/1.1414882
10.1007/BF02191896
10.1016/S0006-3495(94)80715-5
10.1161/01.RES.0000089258.40661.0C
10.1209/epl/i1998-00199-0
10.1016/S0962-8924(00)01793-1
{'key': 'e_1_3_2_36_1', 'first-page': 'H375', 'article-title': 'Anatomical determinants of O2 flux density at coronary capillaries', 'volume': '256', 'author': 'Honig C.R', 'year': '1989', 'journal-title': 'Am. J. Physiol'} / Am. J. Physiol / Anatomical determinants of O2 flux density at coronary capillaries by Honig C.R (1989)
10.1007/978-1-4615-2468-7_117
10.1006/jmcc.1997.0392
10.1152/ajpcell.00159.2003
10.2741/1352
10.1006/excr.2000.5044
10.1103/PhysRevLett.94.128701
10.1152/physrev.1992.72.2.369
10.1242/jcs.00360
10.1073/pnas.0531397100
10.1038/35075138
10.1073/pnas.0408954102
10.1007/BF02584025
10.1083/jcb.101.3.697
10.1016/0022-5193(69)90015-0
Kauffman S.A The origins of order. 1993 New York NY:Oxford University Press.
10.1023/A:1008975105243
10.1161/01.RES.0000085042.89656.C7
10.1161/01.RES.0000091364.90121.0C
10.1242/jcs.112.19.3249 / J. Cell Sci / Tensional forces in fibrillar extracellular matrices control directional capillary sprouting by Korff T (1999)
10.1152/ajpcell.1999.277.6.C1277
10.1083/jcb.200207174
10.1083/jcb.143.6.1735
10.1083/jcb.83.3.576
10.1167/iovs.03-1335
10.1161/01.RES.0000046452.67724.B8
10.1073/pnas.94.3.849
10.1038/90222
10.1161/01.RES.85.11.1046
10.1016/S1534-5807(04)00075-9
10.1038/35023621
10.1242/dev.121.10.3131 / Development / The dorsal involuting marginal zone stiffens anisotropically during its convergent extension in the gastrula of Xenopus laevis by Moore S.W (1995)
10.1007/BF01872883
10.1006/excr.1997.3628
10.1242/jcs.114.5.941 / J. Cell Sci / Integrin regulation of cell–cell adhesion during epithelial tubule formation by Ojakian G.K (2001)
10.1016/S0014-2999(01)00856-1
10.1096/fj.02-0038com
{'key': 'e_1_3_2_73_1', 'first-page': '53', 'article-title': 'Molecular aspects of regulation of cardiac contraction', 'volume': '44', 'author': 'Pelouch V', 'year': '1995', 'journal-title': 'Physiol. Res'} / Physiol. Res / Molecular aspects of regulation of cardiac contraction by Pelouch V (1995)
10.1152/ajpcell.00280.2003
10.1152/ajpheart.2001.281.6.H2425
10.1002/cm.970280102
10.1161/hh1101.091862
10.1172/JCI114957
10.1152/jappl.2000.88.3.1127
10.1152/ajpcell.00435.2001
10.1002/j.1460-2075.1993.tb05813.x
10.1016/S0021-9258(19)50052-7 / J. Biol. Chem / Molecular characterization of the stretch-induced adaptation of cultured cardiac cells. An in vitro model of load-induced cardiac hypertrophy by Sadoshima J (1992)
10.1161/01.RES.73.1.172
10.1006/jmcc.1997.0438
10.1126/science.8171320
10.1161/01.CIR.102.suppl_3.III-22
10.1161/01.RES.80.2.281
10.1113/jphysiol.1996.sp021316
10.1126/science.8097594
{'key': 'e_1_3_2_90_1', 'first-page': 'H203', 'article-title': 'Cytoskeleton modulates gating of voltage-dependent sodium channel in heart', 'volume': '269', 'author': 'Undrovinas A.I', 'year': '1995', 'journal-title': 'Am. J. Physiol'} / Am. J. Physiol / Cytoskeleton modulates gating of voltage-dependent sodium channel in heart by Undrovinas A.I (1995)
10.1126/science.7684161
10.1111/j.1469-7793.2000.t01-1-00057.x
10.1073/pnas.141199598
10.1002/cm.10037
10.1242/jcs.113.22.3979 / J. Cell Sci / Adhesion-dependent control of matrix metalloproteinase-2 activation in human capillary endothelial cells by Yan L (2000)
10.1114/1.1623487
10.1161/01.RES.87.4.316

Dates

Type	When
Created	18 years, 2 months ago (June 25, 2007, 12:45 p.m.)
Deposited	2 years, 3 months ago (May 12, 2023, 12:18 p.m.)
Indexed	2 days, 20 hours ago (Aug. 31, 2025, 6:30 a.m.)
Issued	18 years, 2 months ago (June 22, 2007)
Published	18 years, 2 months ago (June 22, 2007)
Published Online	18 years, 2 months ago (June 22, 2007)
Published Print	18 years ago (Aug. 29, 2007)

Funders 0

None

BibTeX

@article{Parker_2007, title={Extracellular matrix, mechanotransduction and structural hierarchies in heart tissue engineering}, volume={362}, ISSN={1471-2970}, url={http://dx.doi.org/10.1098/rstb.2007.2114}, DOI={10.1098/rstb.2007.2114}, number={1484}, journal={Philosophical Transactions of the Royal Society B: Biological Sciences}, publisher={The Royal Society}, author={Parker, Kevin K and Ingber, Donald E}, year={2007}, month=jun, pages={1267–1279} }

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