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The contribution of cellular mechanotransduction to cardiomyocyte form and function

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Abstract

Myocardial development is regulated by an elegantly choreographed ensemble of signaling events mediated by a multitude of intermediates that take a variety of forms. Cellular differentiation and maturation are a subset of vertically integrated processes that extend over several spatial and temporal scales to create a well-defined collective of cells that are able to function cooperatively and reliably at the organ level. Early efforts to understand the molecular mechanisms of cardiomyocyte fate determination focused primarily on genetic and chemical mediators of this process. However, increasing evidence suggests that mechanical interactions between the extracellular matrix (ECM) and cell surface receptors as well as physical interactions between neighboring cells play important roles in regulating the signaling pathways controlling the developmental processes of the heart. Interdisciplinary efforts have made it apparent that the influence of the ECM on cellular behavior occurs through a multitude of physical mechanisms, such as ECM boundary conditions, elasticity, and the propagation of mechanical signals to intracellular compartments, such as the nucleus. In addition to experimental studies, a number of mathematical models have been developed that attempt to capture the interplay between cells and their local microenvironment and the influence these interactions have on cellular self-assembly and functional behavior. Nevertheless, many questions remain unanswered concerning the mechanism through which physical interactions between cardiomyocytes and their environment are translated into biochemical cellular responses and how these signaling modalities can be utilized in vitro to fabricate myocardial tissue constructs from stem cell-derived cardiomyocytes that more faithfully represent their in vivo counterpart. These studies represent a broad effort to characterize biological form as a conduit for information transfer that spans the nanometer length scale of proteins to the meter length scale of the patient and may yield new insights into the contribution of mechanotransduction into heart development and disease.

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References

  • Alenghat FJ, Ingber DE, Ingber DE (2002) Mechanotransduction: all signals point to cytoskeleton, matrix, and integrins. Sci STKE 2002(119): pe6

    Google Scholar 

  • Alford PW, Nesmith AP, Seywerd JN, Grosberg A, Parker KK (2011) Vascular smooth muscle contractility depends on cell shape. Integr Biol (Camb) 3(11): 1063–1070

    Google Scholar 

  • Androutsellis-Theotokis A, Leker RR, Soldner F, Hoeppner DJ, Ravin R, Poser SW, Rueger MA, Bae S-K, Kittappa R, McKay RDG (2006) Notch signalling regulates stem cell numbers in vitro and in vivo. Nature 442(7104): 823–826

    Google Scholar 

  • Arciniegas E, Frid MG, Douglas IS, Stenmark KR (2007) Perspectives on endothelial-to-mesenchymal transition: potential contribution to vascular remodeling in chronic pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 293(1): L1–L8

    Google Scholar 

  • Auman HJ, Coleman H, Riley HE, Olale F, Tsai H-J, Yelon D (2007) Functional modulation of cardiac form through regionally confined cell shape changes. PLoS Biol 5(3): e53

    Google Scholar 

  • Bajaj P, Tang X, Saif TA, Bashir R (2010) Stiffness of the substrate influences the phenotype of embryonic chicken cardiac myocytes. J Biomed Mater Res A 95(4): 1261–1269

    Google Scholar 

  • Balaban NQ, Schwarz US, Riveline D, Goichberg P, Tzur G, Sabanay I, Mahalu D, Safran S, Bershadsky A, Addadi L, Geiger B (2001) Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates. Nat Cell Biol 3(5): 466–472

    Google Scholar 

  • Balachandran K, Alford PW, Wylie-Sears J, Goss JA, Grosberg A, Bischoff J, Aikawa E, Levine RA, Parker KK (2011) Cyclic strain induces dual-mode endothelial-mesenchymal transformation of the cardiac valve. Proc Natl Acad Sci USA 108(50): 19943–19948

    Google Scholar 

  • Belkin AM, Zhidkova NI, Balzac F, Altruda F, Tomatis D, Maier A, Tarone G, Koteliansky VE, Burridge K (1996) Beta 1D integrin displaces the beta 1A isoform in striated muscles: localization at junctional structures and signaling potential in nonmuscle cells. J Cell Biol 132(1–2): 211–226

    Google Scholar 

  • Bhana B, Iyer RK, Chen WLK, Zhao R, Sider KL, Likhitpanichkul M, Simmons CA, Radisic M (2010) Influence of substrate stiffness on the phenotype of heart cells. Biotechnol Bioeng 105(6): 1148–1160

    Google Scholar 

  • Boateng SY, Belin RJ, Geenen DL, Margulies KB, Martin JL, Hoshijima M, Tombe PP, Russell B (2007) Cardiac dysfunction and heart failure are associated with abnormalities in the subcellular distribution and amounts of oligomeric muscle LIM protein. Am J Physiol Heart Circ Physiol 292(1): H259–H269

    Google Scholar 

  • Boni A, Urbanek K, Nascimbene A, Hosoda T, Zheng H, Delucchi F, Amano K, Gonzalez A, Vitale S, Ojaimi C, Rizzi R, Bolli R, Yutzey KE, Rota M, Kajstura J, Anversa P, Leri A (2008) Notch1 regulates the fate of cardiac progenitor cells. Proc Natl Acad Sci USA 105(40): 15529–15534

    Google Scholar 

  • Brancaccio M, Fratta L, Notte A, Hirsch E, Poulet R, Guazzone S, De Acetis M, Vecchione C, Marino G, Altruda F, Silengo L, Tarone G, Lembo G (2003) Melusin, a muscle-specific integrin beta1-interacting protein, is required to prevent cardiac failure in response to chronic pressure overload. Nat Med 9(1): 68–75

    Google Scholar 

  • Brancaccio M, Guazzone S, Menini N, Sibona E, Hirsch E, De Andrea M, Rocchi M, Altruda F, Tarone G, Silengo L (1999) Melusin is a new muscle-specific interactor for beta(1) integrin cytoplasmic domain. J Biol Chem 274(41): 29282–29288

    Google Scholar 

  • Brangwynne CP, Koenderink GH, Mackintosh FC, Weitz DA (2008) Nonequilibrium microtubule fluctuations in a model cytoskeleton. Phys Rev Lett 100(11): 118104

    Google Scholar 

  • Bray M-A, Sheehy SP, Parker KK (2008) Sarcomere alignment is regulated by myocyte shape. Cell Motil Cytoskeleton 65(8): 641–651

    Google Scholar 

  • Bray M-AP, Adams WJ, Geisse NA, Feinberg AW, Sheehy SP, Parker KK (2009) Nuclear morphology and deformation in engineered cardiac myocytes and tissues. Biomaterials 31(19): 5143–5150

    Google Scholar 

  • Brock A, Chang E, Ho CC, LeDuc P, Jiang XY, Whitesides GM, Ingber DE (2003) Geometric determinants of directional cell motility revealed using microcontact printing. Langmuir 19(5): 1611–1617. doi:10.1021/la026394k

    Google Scholar 

  • Burridge K, Chrzanowska-Wodnicka M (1996) Focal adhesions, contractility, and signaling. Annu Rev Cell Dev Biol 12: 463–518

    Google Scholar 

  • Bursac N, Parker KK, Iravanian S, Tung L (2002) Cardiomyocyte cultures with controlled macroscopic anisotropy: a model for functional electrophysiological studies of cardiac muscle. Circ Res 91(12): e45–e54

    Google Scholar 

  • Cadre BM, Qi M, Eble DM, Shannon TR, Bers DM, Samarel AM (1998) Cyclic stretch down-regulates calcium transporter gene expression in neonatal rat ventricular myocytes. J Mol Cell Cardiol 30(11): 2247–2259

    Google Scholar 

  • Carver W, Price RL, Raso DS, Terracio L, Borg TK (1994) Distribution of beta-1 integrin in the developing rat heart. J Histochem Cytochem 42(2): 167–175

    Google Scholar 

  • Chen CS, Mrksich M, Huang S, Whitesides GM, Ingber DE (1997) Geometric control of cell life and death. Science 276(5317): 1425–1428

    Google Scholar 

  • Chen CS, Tan J, Tien J (2004) Mechanotransduction at cell-matrix and cell-cell contacts. Annu Rev Biomed Eng 6: 275–302

    Google Scholar 

  • Chien KR, Domian IJ, Parker KK (2008) Cardiogenesis and the complex biology of regenerative cardiovascular medicine. Science 322(5907): 1494–1497

    Google Scholar 

  • Chung C-Y, Bien H, Entcheva E (2007) The role of cardiac tissue alignment in modulating electrical function. J Cardiovasc Electrophysiol 18(12): 1323–1329

    Google Scholar 

  • Combs MD, Yutzey KE (2009) Heart valve development: regulatory networks in development and disease. Circ Res 105(5): 408–421

    Google Scholar 

  • Dahl KN, Ribeiro AJS, Lammerding J (2008) Nuclear shape, mechanics, and mechanotransduction. Circ Res 102(11): 1307–1318

    Google Scholar 

  • Damon BJ, Remond MC, Bigelow MR, Trusk TC, Xie W, Perucchio R, Sedmera D, Denslow S, Thompson RP (2009) Patterns of muscular strain in the embryonic heart wall. Dev Dyn 238(6): 1535–1546

    Google Scholar 

  • Melker AA, Sonnenberg A (1999) Integrins: alternative splicing as a mechanism to regulate ligand binding and integrin signaling events. Bioessays 21(6): 499–509

    Google Scholar 

  • Deshpande VS, McMeeking RM, Evans AG (2006) pp 14015–14020. doi:10.1073/pnas.0605837103

    Google Scholar 

  • Deshpande VS, Mrksich M, McMeeking RM, Evans AG (2008) pp 1484–1510. doi:10.1016/j.jmps.2007.08.006

    MATH  Google Scholar 

  • Discher DE, Mooney DJ, Zandstra PW (2009) Growth factors, matrices, and forces combine and control stem cells. Science 324(5935): 1673–1677. doi: 10.1126/science.1171643

    Google Scholar 

  • Engler AJ, Carag-Krieger C, Johnson CP, Raab M, Tang HY, Speicher DW, Sanger JW, Sanger JM, Discher DE (2008) Embryonic cardiomyocytes beat best on a matrix with heart-like elasticity: scar-like rigidity inhibits beating. J Cell Sci 121(22): 3794–3802. doi:10.1242/jcs.029678

    Google Scholar 

  • Engler AJ, Sen S, Sweeney HL, Discher DE (2006) Matrix elasticity directs stem cell lineage specification. Cell 126(4): 677–689. doi:10.1016/j.cell.2006.06.044

    Google Scholar 

  • Evans SM, Yelon D, Conlon FL, Kirby ML (2010) Myocardial lineage development. Circ Res 107(12): 1428–1444

    Google Scholar 

  • Farhadian F, Contard F, Corbier A, Barrieux A, Rappaport L, Samuel JL (1995) Fibronectin expression during physiological and pathological cardiac growth. J Mol Cell Cardiol 27(4): 981–990

    Google Scholar 

  • Fletcher DA, Mullins D (2010) Cell mechanics and the cytoskeleton. Nature 463(7280): 485–492. doi:10.1038/nature08908

    Google Scholar 

  • Frank D, Kuhn C, Brors B, Hanselmann C, Ludde M, Katus HA, Frey N (2008) Gene expression pattern in biomechanically stretched cardiomyocytes: evidence for a stretch-specific gene program. Hypertension 51(2): 309–318

    Google Scholar 

  • Frey N, Olson EN (2003) Cardiac hypertrophy: the good, the bad, and the ugly. Annu Rev Physiol 65: 45–79

    Google Scholar 

  • Fu J, Wang Y-K, Yang MT, Desai RA, Yu X, Liu Z, Chen CS (2010) Mechanical regulation of cell function with geometrically modulated elastomeric substrates. Nat Methods 7(9): 733–736

    Google Scholar 

  • Geisse NA, Sheehy SP, Parker KK (2009) Control of myocyte remodeling in vitro with engineered substrates. In Vitro Cell Dev Biol Anim 45(7): 343–350

    Google Scholar 

  • Georges PC, Janmey PA (2005) Cell type-specific response to growth on soft materials. J Appl Physiol 98(4): 1547–1553

    Google Scholar 

  • Gessert S, Kuhl M (2010) The multiple phases and faces of wnt signaling during cardiac differentiation and development. Circ Res 107(2): 186–199

    Google Scholar 

  • Gjorevski N, Nelson CM (2009) Bidirectional extracellular matrix signaling during tissue morphogenesis. Cytokine Growth Factor Rev 20(5-6): 459–465

    Google Scholar 

  • Goktepe S, Abilez OJ, Parker KK, Kuhl E (2010) A multiscale model for eccentric and concentric cardiac growth through sarcomerogenesis. J Theor Biol 265(3): 433–442

    Google Scholar 

  • Gopalan SM, Flaim C, Bhatia SN, Hoshijima M, Knoell R, Chien KR, Omens JH, McCulloch AD (2003) Anisotropic stretch-induced hypertrophy in neonatal ventricular myocytes micropatterned on deformable elastomers. Biotechnol Bioeng 81(5): 578–587

    Google Scholar 

  • Gourdie RG, Green CR, Severs NJ, Thompson RP (1992) Immunolabelling patterns of gap junction connexins in the developing and mature rat heart. Anat Embryol (Berl) 185(4): 363–378

    Google Scholar 

  • Grosberg A, Kuo P-L, Guo C-L, Geisse NA, Bray M-A, Adams WJ, Sheehy SP, Parker KK (2011) Self-organization of muscle cell structure and function. PLoS Comput Biol 7(2): e1001088

    Google Scholar 

  • Guilak F, Cohen DM, Estes BT, Gimble JM, Liedtke W, Chen CS (2009) Control of stem cell fate by physical interactions with the extracellular matrix. Cell Stem Cell 5(1): 17–26

    Google Scholar 

  • Heineke J, Molkentin JD (2006) Regulation of cardiac hypertrophy by intracellular signalling pathways. Nat Rev Mol Cell Biol 7(8): 589–600

    Google Scholar 

  • Heineke J, Ruetten H, Willenbockel C, Gross SC, Naguib M, Schaefer A, Kempf T, Hilfiker-Kleiner D, Caroni P, Kraft T, Kaiser RA, Molkentin JD, Drexler H, Wollert KC (2005) Attenuation of cardiac remodeling after myocardial infarction by muscle LIM protein-calcineurin signaling at the sarcomeric Z-disc. Proc Natl Acad Sci USA 102(5): 1655–1660

    Google Scholar 

  • Hilenski LL, Ma XH, Vinson N, Terracio L, Borg TK (1992) The role of beta 1 integrin in spreading and myofibrillogenesis in neonatal rat cardiomyocytes in vitro. Cell Motil Cytoskeleton 21(2): 87–100

    Google Scholar 

  • Hornberger LK, Singhroy S, Cavalle-Garrido T, Tsang W, Keeley F, Rabinovitch M (2000) Synthesis of extracellular matrix and adhesion through beta(1) integrins are critical for fetal ventricular myocyte proliferation. Circ Res 87(6): 508–515

    Google Scholar 

  • Hove JR, Koster RW, Forouhar AS, Acevedo-Bolton G, Fraser SE, Gharib M (2003) Intracardiac fluid forces are an essential epigenetic factor for embryonic cardiogenesis. Nature 421(6919): 172–177

    Google Scholar 

  • Huebsch N, Arany PR, Mao AS, Shvartsman D, Ali OA, Bencherif SA, Rivera-Feliciano J, Mooney DJ (2010) Harnessing traction-mediated manipulation of the cell/matrix interface to control stem-cell fate. Nat Mater 9(6): 518–526. doi:10.1038/nmat2732

    Google Scholar 

  • Ingber DE (1993) The riddle of morphogenesis: a question of solution chemistry or molecular cell engineering. Cell 75(7): 1249–1252

    Google Scholar 

  • Ingber DE (1997) Tensegrity: the architectural basis of cellular mechanotransduction. Annu Rev Physiol 59: 575–599

    Google Scholar 

  • Ingber DE (2002) Mechanical signaling and the cellular response to extracellular matrix in angiogenesis and cardiovascular physiology. Circ Res 91(10): 877–887

    Google Scholar 

  • Ingber DE (2006a) Cellular mechanotransduction: putting all the pieces together again. Faseb J 20(7): 811–827

    Google Scholar 

  • Ingber DE (2006b) Mechanical control of tissue morphogenesis during embryological development. Int J Dev Biol 50(2–3): 255–266

    Google Scholar 

  • Itasaki N, Nakamura H, Sumida H, Yasuda M (1991) Actin bundles on the right side in the caudal part of the heart tube play a role in dextro-looping in the embryonic chick heart. Anat Embryol (Berl) 183(1): 29–39

    Google Scholar 

  • Jacot JG, Martin JC, Hunt DL (2010) Mechanobiology of cardiomyocyte development. J Biomech 43(1): 93–98

    Google Scholar 

  • Jacot JG, McCulloch AD, Omens JH (2008) Substrate stiffness affects the functional maturation of neonatal rat ventricular myocytes. Biophys J 95(7): 3479–3487

    Google Scholar 

  • Jamora C, DasGupta R, Kocieniewski P, Fuchs E (2003) Links between signal transduction, transcription and adhesion in epithelial bud development. Nature 422(6929): 317–322. doi:10.1038/nature01458

    Google Scholar 

  • Keller RS, Shai SY, Babbitt CJ, Pham CG, Solaro RJ, Valencik ML, Loftus JC, Ross RS (2001) Disruption of integrin function in the murine myocardium leads to perinatal lethality, fibrosis, and abnormal cardiac performance. Am J Pathol 158(3): 1079–1090

    Google Scholar 

  • Knoll R, Hoshijima M, Hoffman HM, Person V, Lorenzen-Schmidt I, Bang M-L, Hayashi T, Shiga N, Yasukawa H, Schaper W, McKenna W, Yokoyama M, Schork NJ, Omens JH, McCulloch AD, Kimura A, Gregorio CC, Poller W, Schaper J, Schultheiss HP, Chien KR (2002) The cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathy. Cell 111(7): 943–955

    Google Scholar 

  • Kresh JY, Chopra A (2011) Intercellular and extracellular mechanotransduction in cardiac myocytes. Pflugers Arch 462(1): 75–87

    Google Scholar 

  • Kruger M, Linke WA (2009) Titin-based mechanical signalling in normal and failing myocardium. J Mol Cell Cardiol 46(4): 490–498

    Google Scholar 

  • Kuwahara K, Barrientos T, Pipes GCT, Li S, Olson EN (2005) Muscle-specific signaling mechanism that links actin dynamics to serum response factor. Mol Cell Biol 25(8): 3173–3181

    Google Scholar 

  • Kuwahara K, Teg Pipes GC, McAnally J, Richardson JA, Hill JA, Bassel-Duby R, Olson EN (2007) Modulation of adverse cardiac remodeling by STARS, a mediator of MEF2 signaling and SRF activity. J Clin Invest 117(5): 1324–1334

    Google Scholar 

  • Kwon C, Qian L, Cheng P, Nigam V, Arnold J, Srivastava D (2009) A regulatory pathway involving Notch1/beta-catenin/Isl1 determines cardiac progenitor cell fate. Nat Cell Biol 11(8): 951–957

    Google Scholar 

  • Lange S, Auerbach D, McLoughlin P, Perriard E, Schafer BW, Perriard J-C, Ehler E (2002) Subcellular targeting of metabolic enzymes to titin in heart muscle may be mediated by DRAL/FHL-2. J Cell Sci 115(Pt 24): 4925–4936

    Google Scholar 

  • Lange S, Xiang F, Yakovenko A, Vihola A, Hackman P, Rostkova E, Kristensen J, Brandmeier B, Franzen G, Hedberg B, Gunnarsson LG, Hughes SM, Marchand S, Sejersen T, Richard I, Edstrom L, Ehler E, Udd B, Gautel M (2005) The kinase domain of titin controls muscle gene expression and protein turnover. Science 308(5728): 1599–1603

    Google Scholar 

  • Latacha KS, Remond MC, Ramasubramanian A, Chen AY, Elson EL, Taber LA (2005) Role of actin polymerization in bending of the early heart tube. Dev Dyn 233(4): 1272–1286

    Google Scholar 

  • Latimer DC, Roth BJ, Parker KK (2003) Analytical model for predicting mechanotransduction effects in engineered cardiac tissue. Tissue Eng 9(2): 283–289

    Google Scholar 

  • Linke WA (2008) Sense and stretchability: the role of titin and titin-associated proteins in myocardial stress-sensing and mechanical dysfunction. Cardiovasc Res 77(4): 637–648

    Google Scholar 

  • Liu Z, Tan JL, Cohen DM, Yang MT, Sniadecki NJ, Ruiz SA, Nelson CM, Chen CS (2010) Mechanical tugging force regulates the size of cell-cell junctions. Proc Natl Acad Sci USA 107(22): 9944–9949

    Google Scholar 

  • Mack CP, Somlyo AV, Hautmann M, Somlyo AP, Owens GK (2001) Smooth muscle differentiation marker gene expression is regulated by RhoA-mediated actin polymerization. J Biol Chem 276(1): 341–347

    Google Scholar 

  • Mammoto A, Connor KM, Mammoto T, Yung CW, Huh D, Aderman CM, Mostoslavsky G, Smith LEH, Ingber DE (2009) A mechanosensitive transcriptional mechanism that controls angiogenesis. Nature 457(7233): 1103–1108

    Google Scholar 

  • Manasek FJ, Burnside MB, Waterman RE (1972) Myocardial cell shape change as a mechanism of embryonic heart looping. Dev Biol 29(4): 349–371

    Google Scholar 

  • Manasek FJ, Monroe RG (1972) Early cardiac morphogenesis is independent of function. Dev Biol 27(4): 584–588

    Google Scholar 

  • Maniotis AJ, Bojanowski K, Ingber DE (1997) Mechanical continuity and reversible chromosome disassembly within intact genomes removed from living cells. J Cell Biochem 65(1): 114–130

    Google Scholar 

  • Maniotis AJ, Chen CS, Ingber DE (1997) Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure. Proc Natl Acad Sci USA 94(3): 849–854

    Google Scholar 

  • Matthews BD, Overby DR, Mannix R, Ingber DE (2006) Cellular adaptation to mechanical stress: role of integrins, Rho, cytoskeletal tension and mechanosensitive ion channels. J Cell Sci 119(Pt 3): 508–518

    Google Scholar 

  • McCain ML, Desplantez T, Geisse NA, Rothen-Rutishauser B, Oberer H, Parker KK, Kleber AG (2012) Cell-to-cell coupling in engineered pairs of rat ventricular cardiomyocytes: relation between Cx43 immunofluorescence and intercellular electrical conductance. Am J Physiol Heart Circ Physiol 302(2): H443–H450

    Google Scholar 

  • McCain ML, Parker KK (2011) Mechanotransduction: the role of mechanical stress, myocyte shape, and cytoskeletal architecture on cardiac function. Pflugers Arch 462(1): 89–104

    Google Scholar 

  • Meyer CJ, Alenghat FJ, Rim P, Fong JH, Fabry B, Ingber DE (2000) Mechanical control of cyclic AMP signalling and gene transcription through integrins. Nat Cell Biol 2(9): 666–668

    Google Scholar 

  • Miller LA (2011) Fluid dynamics of ventricular filling in the embryonic heart. Cell Biochem Biophys 61(1): 33–45

    Google Scholar 

  • Miyake Y, Inoue N, Nishimura K, Kinoshita N, Hosoya H, Yonemura S (2006) Actomyosin tension is required for correct recruitment of adherens junction components and zonula occludens formation. Exp Cell Res 312(9): 1637–1650

    Google Scholar 

  • Moore KA, Polte T, Huang S, Shi B, Alsberg E, Sunday ME, Ingber DE (2005) Control of basement membrane remodeling and epithelial branching morphogenesis in embryonic lung by Rho and cytoskeletal tension. Dev Dyn 232(2): 268–281

    Google Scholar 

  • Mrksich M, Chen CS, Xia Y, Dike LE, Ingber DE, Whitesides GM (1996) Controlling cell attachment on contoured surfaces with self-assembled monolayers of alkanethiolates on gold. Proc Natl Acad Sci USA 93(20): 10775–10778

    Google Scholar 

  • Mrksich M, Dike LE, Tien J, Ingber DE, Whitesides GM (1997) Using microcontact printing to pattern the attachment of mammalian cells to self-assembled monolayers of alkanethiolates on transparent films of gold and silver. Exp Cell Res 235(2): 305–313

    Google Scholar 

  • Nelson WJ, Nusse R (2004a) Convergence of Wnt, beta-catenin, and cadherin pathways. Science 303(5663): 1483–1487

    Google Scholar 

  • Nelson WJ, Nusse R (2004b) Convergence of Wnt, beta-catenin, and cadherin pathways. Science 303(5663): 1483–1487

    Google Scholar 

  • Niessen CM, Leckband D, Yap AS (2011) Tissue organization by cadherin adhesion molecules: dynamic molecular and cellular mechanisms of morphogenetic regulation. Physiol Rev 91(2): 691–731

    Google Scholar 

  • Novak IL, Slepchenko BM, Mogilner A, Loew LM (2004) Cooperativity between cell contractility and adhesion. Phys Rev Lett 93(26 Pt 1): 268109

    Google Scholar 

  • Olson EN, Nordheim A (2010) Linking actin dynamics and gene transcription to drive cellular motile functions. Nat Rev Mol Cell Biol 11(5): 353–365

    Google Scholar 

  • Parker KK, Brock AL, Brangwynne C, Mannix RJ, Wang N, Ostuni E, Geisse NA, Adams JC, Whitesides GM, Ingber DE (2002) Directional control of lamellipodia extension by constraining cell shape and orienting cell tractional forces. Faseb J 16(10): 1195–1204

    Google Scholar 

  • Parker KK, Ingber DE (2007) Extracellular matrix, mechanotransduction and structural hierarchies in heart tissue engineering. Philos Trans R Soc Lond B Biol Sci 362(1484): 1267–1279

    Google Scholar 

  • Parker KK, Tan J, Chen CS, Tung L (2008) Myofibrillar architecture in engineered cardiac myocytes. Circ Res 103(4): 340–342

    Google Scholar 

  • Paszek MJ, Boettiger D, Weaver VM, Hammer DA (2009) Integrin clustering is driven by mechanical resistance from the glycocalyx and the substrate. PLoS Comput Biol 5(12). doi:10.1371/journal.pcbi.1000604

  • Pelham RJ Jr, Wang Yl (1997) Cell locomotion and focal adhesions are regulated by substrate flexibility. Proc Natl Acad Sci USA 94(25): 13661–13665

    Google Scholar 

  • Peters NS, Severs NJ, Rothery SM, Lincoln C, Yacoub MH, Green CR (1994) Spatiotemporal relation between gap junctions and fascia adherens junctions during postnatal development of human ventricular myocardium. Circulation 90(2): 713–725

    Google Scholar 

  • Pijnappels DA, Schalij MJ, Ramkisoensing AA, Tuyn J, Vries AAF, Laarse A, Ypey DL, Atsma DE (2008) Forced alignment of mesenchymal stem cells undergoing cardiomyogenic differentiation affects functional integration with cardiomyocyte cultures. Circ Res 103(2): 167–176

    Google Scholar 

  • Pong T, Adams WJ, Bray M-A, Feinberg AW, Sheehy SP, Werdich AA, Parker KK (2011) Hierarchical architecture influences calcium dynamics in engineered cardiac muscle. Exp Biol Med (Maywood) 236(3): 366–373

    Google Scholar 

  • Price RL, Chintanowonges C, Shiraishi I, Borg TK, Terracio L (1996) Local and regional variations in myofibrillar patterns in looping rat hearts. Anat Rec 245(1): 83–93

    Google Scholar 

  • Price RL, Nakagawa M, Terracio L, Borg TK (1992) Ultrastructural localization of laminin on in vivo embryonic, neonatal, and adult rat cardiac myocytes and in early rat embryos raised in whole-embryo culture. J Histochem Cytochem 40(9): 1373–1381

    Google Scholar 

  • Puchner EM, Alexandrovich A, Kho AL, Hensen U, Schafer LV, Brandmeier B, Grater F, Grubmuller H, Gaub HE, Gautel M (2008) Mechanoenzymatics of titin kinase. Proc Natl Acad Sci USA 105(36): 13385–13390

    Google Scholar 

  • Rao TP, Kuhl M (2010) An updated overview on Wnt signaling pathways: a prelude for more. Circ Res 106(12): 1798–1806

    Google Scholar 

  • Ross RS, Borg TK (2001) Integrins and the myocardium. Circ Res 88(11): 1112–1119

    Google Scholar 

  • Saffitz JE (2005) Dependence of electrical coupling on mechanical coupling in cardiac myocytes: insights gained from cardiomyopathies caused by defects in cell-cell connections. Ann N Y Acad Sci 1047: 336–344

    Google Scholar 

  • Saffitz JE, Kleber AG (2004) Effects of mechanical forces and mediators of hypertrophy on remodeling of gap junctions in the heart. Circ Res 94(5): 585–591

    Google Scholar 

  • Salameh A, Wustmann A, Karl S, Blanke K, Apel D, Rojas-Gomez D, Franke H, Mohr FW, Janousek J, Dhein S (2010) Cyclic mechanical stretch induces cardiomyocyte orientation and polarization of the gap junction protein connexin43. Circ Res 106(10): 1592–1602

    Google Scholar 

  • Samarakoon R, Higgins PJ (2002) MEK/ERK pathway mediates cell-shape-dependent plasminogen activator inhibitor type 1 gene expression upon drug-induced disruption of the microfilament and microtubule networks. J Cell Sci 115(Pt 15): 3093–3103

    Google Scholar 

  • Samarel AM (2005) Costameres, focal adhesions, and cardiomyocyte mechanotransduction. Am J Physiol Heart Circ Physiol 289(6): H2291–H2301

    Google Scholar 

  • Samuel JL, Farhadian F, Sabri A, Marotte F, Robert V, Rappaport L (1994) Expression of fibronectin during rat fetal and postnatal development: an in situ hybridisation and immunohistochemical study. Cardiovasc Res 28(11): 1653–1661

    Google Scholar 

  • Santhanakrishnan A, Miller LA (2011) Fluid dynamics of heart development. Cell Biochem Biophys 61(1): 1–22

    Google Scholar 

  • Schwartz MA, Ginsberg MH (2002) Networks and crosstalk: integrin signalling spreads. Nat Cell Biol 4(4): E65–E68

    Google Scholar 

  • Schwartz MA, Schaller MD, Ginsberg MH (1995) Integrins: emerging paradigms of signal transduction. Annu Rev Cell Dev Biol 11: 549–599

    Google Scholar 

  • Shai S-Y, Harpf AE, Babbitt CJ, Jordan MC, Fishbein MC, Chen J, Omura M, Leil TA, Becker KD, Jiang M, Smith DJ, Cherry SR, Loftus JC, Ross RS (2002) Cardiac myocyte-specific excision of the beta1 integrin gene results in myocardial fibrosis and cardiac failure. Circ Res 90(4): 458–464

    Google Scholar 

  • Shanker AJ, Yamada K, Green KG, Yamada KA, Saffitz JE (2005) Matrix-protein-specific regulation of Cx43 expression in cardiac myocytes subjected to mechanical load. Circ Res 96(5): 558–566

    Google Scholar 

  • Sheehy SP, Huang S, Parker KK (2009) Time-warped comparison of geneexpression in adaptive and maladaptive cardiac hypertrophy. Circ Cardiovasc Genet 2(2): 116–124

    Google Scholar 

  • Sheikh F, Raskin A, Chu P-H, Lange S, Domenighetti AA, Zheng M, Liang X, Zhang T, Yajima T, Gu Y, Dalton ND, Mahata SK, Dorn GW 2nd, Heller-Brown J, Peterson KL, Omens JH, McCulloch AD, Chen J (2008) An FHL1-containing complex within the cardiomyocyte sarcomeremediates hypertrophic biomechanical stress responses in mice. J Clin Invest 118(12): 3870–3880

    Google Scholar 

  • Simpson DG, Decker ML, Clark WA, Decker RS (1993) Contractile activity and cell-cell contact regulate myofibrillar organization in cultured cardiac myocytes. J Cell Biol 123(2): 323–336

    Google Scholar 

  • Singhvi R, Kumar A, Lopez GP, Stephanopoulos GN, Wang DI, Whitesides GM, Ingber DE (1994) Engineering cell shape and function. Science 264(5159): 696–698

    Google Scholar 

  • Srivastava D, Olson EN (2000) A genetic blueprint for cardiac development. Nature 407(6801): 221–226

    Google Scholar 

  • Taber LA (2001) Biomechanics of cardiovascular development. Annu Rev Biomed Eng 3: 1–25

    Google Scholar 

  • Taber LA, Lin IE, Clark EB (1995) Mechanics of cardiac looping. Dev Dyn 203(1): 42–50

    Google Scholar 

  • Terracio L, Rubin K, Gullberg D, Balog E, Carver W, Jyring R, Borg TK (1991) Expression of collagen binding integrins during cardiac development and hypertrophy. Circ Res 68(3): 734–744

    Google Scholar 

  • Thomas CH, Collier JH, Sfeir CS, Healy KE (2002) Engineering gene expression and protein synthesis by modulation of nuclear shape. Proc Natl Acad Sci USA 99(4): 1972–1977

    Google Scholar 

  • Tobita K, Schroder EA, Tinney JP, Garrison JB, Keller BB (2002) Regional passive ventricular stress-strain relations during development of altered loads in chick embryo. Am J Physiol Heart Circ Physiol 282(6): H2386–H2396

    Google Scholar 

  • Trepat X, Deng L, An SS, Navajas D, Tschumperlin DJ, Gerthoffer WT, Butler JP, Fredberg JJ (2007) Universal physical responses to stretch in the living cell. Nature 447(7144): 592–595

    Google Scholar 

  • Ueno S, Weidinger G, Osugi T, Kohn AD, Golob JL, Pabon L, Reinecke H, Moon RT, Murry CE (2007) Biphasic role for Wnt/beta-catenin signaling in cardiac specification in zebrafish and embryonic stem cells. Proc Natl Acad Sci USA 104(23): 9685–9690

    Google Scholar 

  • Flier A, Gaspar AC, Thorsteinsdottir S, Baudoin C, Groeneveld E, Mummery CL, Sonnenberg A (1997) Spatial and temporal expression of the beta1D integrin during mouse development. Dev Dyn 210(4): 472–486

    Google Scholar 

  • Walsh KB, Parks GE (2002) Changes in cardiac myocyte morphology alter the properties of voltage-gated ion channels. Cardiovasc Res 55(1): 64–75

    Google Scholar 

  • Wang N, Butler JP, Ingber DE (1993) Mechanotransduction across the cell surface and through the cytoskeleton. Science 260(5111): 1124–1127

    Google Scholar 

  • Wang N, Tytell JD, Ingber DE (2009) Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus. Nat Rev Mol Cell Biol 10(1): 75–82

    Google Scholar 

  • Wozniak MA, Chen CS (2009) Mechanotransduction in development: a growing role for contractility. Nat Rev Mol Cell Biol 10(1): 34–43

    Google Scholar 

  • Yamada K, Green KG, Samarel AM, Saffitz JE (2005) Distinct pathways regulate expression of cardiac electrical and mechanical junction proteins in response to stretch. Circ Res 97(4): 346–353

    Google Scholar 

  • Yang J-H, Wylie-Sears J, Bischoff J (2008) Opposing actions of Notch1 and VEGF in post-natal cardiac valve endothelial cells. Biochem Biophys Res Commun 374(3): 512–516

    Google Scholar 

  • Yin L, Bien H, Entcheva E (2004) Scaffold topography alters intracellular calcium dynamics in cultured cardiomyocyte networks. Am J Physiol Heart Circ Physiol 287(3): H1276–H1285

    Google Scholar 

  • Zajac AL, Discher DE (2008) Cell differentiation through tissue elasticity-coupled, myosin-driven remodeling. Curr Opin Cell Biol 20(6): 609–615. doi:10.1016/j.ceb.2008.09.006

    Google Scholar 

  • Zhuang J, Yamada KA, Saffitz JE, Kleber AG (2000) Pulsatile stretch remodels cell-to-cell communication in cultured myocytes. Circ Res 87(4): 316–322

    Google Scholar 

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  1. Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, School of Engineering and Applied Sciences, Harvard University, Pierce Hall Rm. 321, 29 Oxford St., Cambridge, MA, 02138, USA

    Sean P. Sheehy, Anna Grosberg & Kevin Kit Parker

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  1. Sean P. Sheehy
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  2. Anna Grosberg
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Correspondence to Kevin Kit Parker.

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Sheehy, S.P., Grosberg, A. & Parker, K.K. The contribution of cellular mechanotransduction to cardiomyocyte form and function. Biomech Model Mechanobiol 11, 1227–1239 (2012). https://doi.org/10.1007/s10237-012-0419-2

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