Cardiomyocytes Sense Matrix Rigidity through a Combination of Muscle and Non-muscle Myosin Contractions

Pandey, Pragati; Hawkes, William; Hu, Junquiang; Megone, William; Gautrot, Julien E.; Anilkumar, Narayana; Zhang, Min; Hirvonen, L; Cox, Susan; Ehler, Elisabeth; Hone, James; Sheetz, Michael P.; Iskratsch, Thomas

doi:10.1016/j.devcel.2017.12.024

Cited by 110 publications

(115 citation statements)

References 87 publications

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“…In this respect, completely crosslinked hydrogels fabricated using three different compositions of biomaterial inks (by varying the amount of GelMA) were analyzed for their compressive strength in order to finalize the optimal concentration of the supporting hydrogel (Figure C,D). In particular, a Young's modulus of 37.3 ± 4.9 kPa was obtained for ink comprising of 5% GelMA, 1% n‐SF and 1% PEGDMA (SPG5) that was in the range of the local modulus of native ECM . The ability to assure the viability of the encapsulated cells in polymer‐based hydrogels requires them to be porous enough that an exchange of nutrients and oxygen can be facilitated.…”

Section: Resultsmentioning

confidence: 99%

Nonmulberry Silk Based Ink for Fabricating Mechanically Robust Cardiac Patches and Endothelialized Myocardium‐on‐a‐Chip Application

Mehrotra

Hirano

Keung

et al. 2020

Adv Funct Materials

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Bioprinting holds great promise toward engineering functional cardiac tissue constructs for regenerative medicine and as drug test models. However, it is highly limited by the choice of inks that require maintaining a balance between the structure and functional properties associated with the cardiac tissue. In this regard, a novel and mechanically robust biomaterial‐ink based on nonmulberry silk fibroin protein is developed. The silk‐based ink demonstrates suitable mechanical properties required in terms of elasticity and stiffness (≈40 kPa) for developing clinically relevant cardiac tissue constructs. The ink allows the fabrication of stable anisotropic scaffolds using a dual crosslinking method, which are able to support formation of aligned sarcomeres, high expression of gap junction proteins as connexin‐43, and maintain synchronously beating of cardiomyocytes. The printed constructs are found to be nonimmunogenic in vitro and in vivo. Furthermore, delving into an innovative method for fabricating a vascularized myocardial tissue‐on‐a‐chip, the silk‐based ink is used as supporting hydrogel for encapsulating human induced pluripotent stem cell derived cardiac spheroids (hiPSC‐CSs) and creating perfusable vascularized channels via an embedded bioprinting technique. The ability is confirmed of silk‐based supporting hydrogel toward maturation and viability of hiPSC‐CSs and endothelial cells, and for applications in evaluating drug toxicity.

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Section: Resultsmentioning

confidence: 99%

Nonmulberry Silk Based Ink for Fabricating Mechanically Robust Cardiac Patches and Endothelialized Myocardium‐on‐a‐Chip Application

Mehrotra

Hirano

Keung

et al. 2020

Adv Funct Materials

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“…As discussed, this was shown by Stout et al, presenting a change in cellular adhesion characteristics based on a synergistic mix of topography and stiffness brought on by CNF doping. An interesting work by Pandey et al illustrates the way native heart tissue mechanical cues induce proliferation, differentiation or fibrosis. It can be inferred that a hierarchy of mechanical cues, simulated by a soft substrate with stiff components, may also be beneficial to cellular growth.…”

Section: Discussion and Open Questions For The Use Of Conductive Tissmentioning

confidence: 99%

Conductive Scaffolds for Cardiac and Neuronal Tissue Engineering: Governing Factors and Mechanisms

Burnstine‐Townley

Eshel

Amdursky

2019

Adv Funct Materials

118

102

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Tissue engineering is a promising therapeutic approach in medicine, targeting the replacement of a diseased tissue with a healthy one grown within an artificial scaffold. Due to the high prevalence of cardiac and brain‐related ailments that involve some necrosis of tissue, cardiac and neuronal tissue engineering are intensely studied fields in regenerative medicine. A growing trend in the use of conductive scaffolds for the growth of these tissues has been witnessed recently. While the results are irrefutable, the mechanism of how an electrically conducting scaffold interacts with an electroactive tissue remains has remained elusive. An up‐to‐date summary of all work done in the field is reported, with a special focus on the specific contribution of the conductive scaffold on the performance of the formed tissue. The cell–scaffold electronic interface is then explored from an electrical engineering perspective. The electronic configuration of the system and the mechanisms and governing factors controlling the ability of a conductive scaffold to support cardiac and neuronal tissues are discussed. Using several simulations, the required conductivity of the scaffold in order for it to be suitable for tissue engineering—which also depends on the nature of the charge carriers—is also discussed.

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“…It has very recently been reported that Fhod1 is involved in mechanosensing of matrix rigidity in cultured cardiomyocytes via regulation of nonmyofibrillar contractions (Pandey et al, ). Considering that Fhod1 is only marginally expressed in the normal heart tissue (as shown here), it may be possible that Fhod1 expression is induced during isolation and/or culture of cardiomyocytes.…”

Section: Discussionmentioning

confidence: 99%

Fhod1, an actin‐organizing formin family protein, is dispensable for cardiac development and function in mice

et al. 2019

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The formin family proteins have the ability to regulate actin filament assembly, thereby functioning in diverse cytoskeletal processes. Fhod3, a cardiac member of the family, plays a crucial role in development and functional maintenance of the heart. Although Fhod1, a protein closely‐related to Fhod3, has been reported to be expressed in cardiomyocytes, the role of Fhod1 in the heart has still remained elusive. To know the physiological role of Fhod1 in the heart, we disrupted the Fhod1 gene in mice by replacement of exon 1 with a lacZ reporter gene. Histological lacZ staining unexpectedly revealed no detectable expression of Fhod1 in the heart, in contrast to intensive staining in the lung, a Fhod1‐containing organ. Consistent with this, expression level of the Fhod1 protein in the heart was below the lower limit of detection of the present immunoblot analysis with three independent anti‐Fhod1 antibodies. Homozygous Fhod1‐null mice did not show any defects in gross and histological appearance of the heart or upregulate fetal cardiac genes that are induced under stress conditions. Furthermore, Fhod1 ablation did not elicit compensatory increase in expression of other formins. Thus, Fhod1 appears to be dispensable for normal development and function of the mouse heart, even if a marginal amount of Fhod1 is expressed in the heart.

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Cardiomyocytes Sense Matrix Rigidity through a Combination of Muscle and Non-muscle Myosin Contractions

Cited by 110 publications

References 87 publications

Nonmulberry Silk Based Ink for Fabricating Mechanically Robust Cardiac Patches and Endothelialized Myocardium‐on‐a‐Chip Application

Nonmulberry Silk Based Ink for Fabricating Mechanically Robust Cardiac Patches and Endothelialized Myocardium‐on‐a‐Chip Application

Conductive Scaffolds for Cardiac and Neuronal Tissue Engineering: Governing Factors and Mechanisms

Fhod1, an actin‐organizing formin family protein, is dispensable for cardiac development and function in mice

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