Cross-bridge cycling gives rise to spatiotemporal heterogeneity of dynamic subcellular mechanics in cardiac myocytes probed with atomic force microscopy

Azeloglu, Evren U.; Costa, Kevin D.

doi:10.1152/ajpheart.00427.2009

Cited by 41 publications

(49 citation statements)

References 46 publications

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“…The cardiomyocyte stiffness on N-cadherin-coated substrate of physiologically realistic stiffness (ϳ10 kPa), measured here as E myocytes ϳ8 kPa, is in agreement with results from other studies showing E NVRM ϳ11 kPa, E myotubes ϳ8 -18 kPa or the native myocardium, which is E ϳ15 Ϫ 30 kPa (3,7,14,15). Other studies have shown that myocardial stiffness is altered dramatically after birth (from ϳ12 kPa to ϳ39 kPa), implicating a commensurate change in substrate stiffness during cardiogenesis (26).…”

Section: Discussionsupporting

confidence: 91%

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Cardiac myocyte remodeling mediated by N-cadherin-dependent mechanosensing

Chopra

Tabdanov

Patel

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

126

184

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Chopra A, Tabdanov E, Patel H, Janmey PA, Kresh JY. Cardiac myocyte remodeling mediated by N-cadherin-dependent mechanosensing. Am J Physiol Heart Circ Physiol 300: H1252-H1266, 2011. First published January 21, 2011 doi:10.1152 doi:10. /ajpheart.00515.2010 adhesions are crucial in maintaining the structural and functional integrity of cardiac cells. Little is known about the mechanosensitivity and mechanotransduction of cell-to-cell interactions. Most studies of cardiac mechanotransduction and myofibrillogenesis have focused on cell-extracellular matrix (ECM)-specific interactions. This study assesses the direct role of intercellular adhesion, specifically that of N-cadherin-mediated mechanotransduction, on the morphology and internal organization of neonatal ventricular cardiac myocytes. The results show that cadherin-mediated cell attachments are capable of eliciting a cytoskeletal network response similar to that of integrinmediated force response and transmission, affecting myofibrillar organization, myocyte shape, and cortical stiffness. Traction forces mediated by N-cadherin were shown to be comparable to those sustained by ECM. The directional changes in predicted traction forces as a function of imposed loads (gel stiffness) provide the added evidence that N-cadherin is a mechanoresponsive adhesion receptor. Strikingly, the mechanical sensitivity response (gain) in terms of the measured cell-spread area as a function of imposed load (adhesive substrate rigidity) was consistently higher for N-cadherin-coated surfaces compared with ECM protein-coated surfaces. In addition, the cytoskeletal architecture of myocytes on an N-cadherin adhesive microenvironment was characteristically different from that on an ECM environment, suggesting that the two mechanotransductive cell adhesion systems may play both independent and complementary roles in myocyte cytoskeletal spatial organization. These results indicate that cell-to-cell-mediated force perception and transmission are involved in the organization and development of cardiac structure and function.cell-to-cell interaction; myofibrillogenesis; extracellular matrix; cell biomechanics NUMEROUS STUDIES IN CELL MECHANOBIOLOGY have shown that the stiffness of the material on which or within which cells grow has sizeable, specific effects on cell morphology, cytoskeletal structure, motility, differentiation, and proliferation (16,39,43,50,62). Mechanical cues, which can act together with or in opposition to chemical stimuli, are potentially associated with pathological conditions that occur in cancer, fibrotic disease, abnormal wound healing, and cardiac remodeling. The mechanical microenvironment of the cell in vivo is defined by its attachment to the extracellular matrix (ECM) and to other cells via forces generated and transmitted across cell-to-cell junctions constituting a network assembly of cells. Nearly all studies of cell mechanobiology in vitro have focused on the attachment of subconfluent cells to ECM ligands such as fibronectin, collagen, and laminin. ...

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Section: Discussionsupporting

confidence: 91%

“…In cardiac disease, especially hypertrophic, dilated cardiac myopathy and at the border zones of an infarct, severe disarray of myocytes in cardiac tissue has been noted (2,3). The spatial disarray of cardiac myocytes is characterized by increased lateral localization of the N-cadherin and gap junctions, which can serve as a trigger of arrhythmias (6).…”

mentioning

confidence: 99%

Cardiac myocyte remodeling mediated by N-cadherin-dependent mechanosensing

Chopra

Tabdanov

Patel

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

126

184

View full text Add to dashboard Cite

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“…CMs are mechanically anisotropic [7][8][9][10] and their main characteristics are their rhythmic beating 11 and their inability to proliferate in the postembryonic stage. 4 A limited number of dead CMs are replaced with new ones 12 through a progenitor pool, and in order for the new CMs to maintain the cardiac function and mechanical demands (i.e., adapt to tissue stresses due to pressure or volume overload) they grow in size by elongating and becoming thicker.…”

Section: Microenvironmental Effect On Cmsmentioning

confidence: 99%

Effect of Substrate Mechanics on Cardiomyocyte Maturation and Growth

Tallawi

Rai

Boccaccını

et al. 2015

Tissue Engineering Part B: Reviews

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Cardiac tissue engineering constructs are a promising therapeutic treatment for myocardial infarction, which is one of the leading causes of death. In order to further advance the development and regeneration of engineered cardiac tissues using biomaterial platforms, it is important to have a complete overview of the effects that substrates have on cardiomyocyte (CM) morphology and function. This article summarizes recent studies that investigate the effect of mechanical cues on the CM differentiation, maturation, and growth. In these studies, CMs derived from embryos, neonates, and mesenchymal stem cells were seeded on different substrates of various elastic modulus. Measuring the contractile function by force production, work output, and calcium handling, it was seen that cell behavior on substrates was optimized when the substrate stiffness mimicked that of the native tissue. The contractile function reflected changes in the sarcomeric protein confirmation and organization that promoted the contractile ability. The analysis of the literature also revealed that, in addition to matrix stiffness, mechanical stimulation, such as stretching the substrate during cell seeding, also played an important role during cell maturation and tissue development.

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“…A 5 × 5 array of 25 indentations, covering an 80 × 80-μm region of tissue, was performed at 3 to 5 sites per heart using a pyramidal AFM probe with a spring constant of 0.07 N/m. AFM experiments were completed within 15 minutes, followed by Hertz contact analysis to determine the apparent elastic modulus of the tissue (56), which yielded a single average modulus value for each heart. For electron microscopy, 16-day-old Fbn1 -/-and Fbn1 -/-mice were euthanized with CO2 and the hearts immediately perfused with saline followed by fixation with 0.5% gluteraldehyde and 0.2% tannic acid in PBS.…”

Section: Methodsmentioning

confidence: 99%

Abnormal muscle mechanosignaling triggers cardiomyopathy in mice with Marfan syndrome

Cook¹,

Carta²,

Bénard³

et al. 2014

J. Clin. Invest.

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121

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Patients with Marfan syndrome (MFS), a multisystem disorder caused by mutations in the gene encoding the extracellular matrix (ECM) protein fibrillin 1, are unusually vulnerable to stress-induced cardiac dysfunction. The prevailing view is that MFS-associated cardiac dysfunction is the result of aortic and/or valvular disease. Here, we determined that dilated cardiomyopathy (DCM) in fibrillin 1-deficient mice is a primary manifestation resulting from ECM-induced abnormal mechanosignaling by cardiomyocytes. MFS mice displayed spontaneous emergence of an enlarged and dysfunctional heart, altered physical properties of myocardial tissue, and biochemical evidence of chronic mechanical stress, including increased angiotensin II type I receptor (AT1R) signaling and abated focal adhesion kinase (FAK) activity. Partial fibrillin 1 gene inactivation in cardiomyocytes was sufficient to precipitate DCM in otherwise phenotypically normal mice. Consistent with abnormal mechanosignaling, normal cardiac size and function were restored in MFS mice treated with an AT1R antagonist and in MFS mice lacking AT1R or β-arrestin 2, but not in MFS mice treated with an angiotensin-converting enzyme inhibitor or lacking angiotensinogen. Conversely, DCM associated with abnormal AT1R and FAK signaling was the sole abnormality in mice that were haploinsufficient for both fibrillin 1 and β1 integrin. Collectively, these findings implicate fibrillin 1 in the physiological adaptation of cardiac muscle to elevated workload.

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Cross-bridge cycling gives rise to spatiotemporal heterogeneity of dynamic subcellular mechanics in cardiac myocytes probed with atomic force microscopy

Cited by 41 publications

References 46 publications

Cardiac myocyte remodeling mediated by N-cadherin-dependent mechanosensing

Cardiac myocyte remodeling mediated by N-cadherin-dependent mechanosensing

Effect of Substrate Mechanics on Cardiomyocyte Maturation and Growth

Abnormal muscle mechanosignaling triggers cardiomyopathy in mice with Marfan syndrome

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