Cardiomyocytes Sense Matrix Rigidity through a Combination of Muscle and Non-muscle Myosin Contractions
| Autor: | Liisa M. Hirvonen, Pragati Pandey, Narayana Anilkumar, James Hone, Thomas Iskratsch, Michael P. Sheetz, Elisabeth Ehler, William Megone, William Hawkes, Junquiang Hu, Min Zhang, Julien E. Gautrot, Susan Cox |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Talin Myocardial Infarction Rigidity (psychology) macromolecular substances heart disease Biology Myosins contractility General Biochemistry Genetics and Molecular Biology Article cardiomyocyte rigidity sensing 03 medical and health sciences Mice Animals Myocytes Cardiac PKC Molecular Biology Cells Cultured Non muscle myosin actomyosin Nonmuscle Myosin Type IIA Cell Biology Extracellular Matrix Rats Mice Inbred C57BL 030104 developmental biology Animals Newborn Biophysics cardiac myosin Female FHOD1 non-muscle myosin Developmental Biology Muscle Contraction Src |
| Zdroj: | Developmental Cell Pandey, P, Hawkes, W, Hu, J, Megone, W V, Gautrot, J, Anilkumar, N, Zhang, M, Hirvonen, L, Cox, S, Ehler, E, Hone, J, Sheetz, M & Iskratsch, T 2018, ' Cardiomyocytes Sense Matrix Rigidity through a Combination of Muscle and Non-muscle Myosin Contractions ', Developmental Cell, vol. 44, no. 3, pp. 326-336 . https://doi.org/10.1016/j.devcel.2017.12.024 |
| ISSN: | 1878-1551 1534-5807 |
| Popis: | Summary Mechanical properties are cues for many biological processes in health or disease. In the heart, changes to the extracellular matrix composition and cross-linking result in stiffening of the cellular microenvironment during development. Moreover, myocardial infarction and cardiomyopathies lead to fibrosis and a stiffer environment, affecting cardiomyocyte behavior. Here, we identify that single cardiomyocyte adhesions sense simultaneous (fast oscillating) cardiac and (slow) non-muscle myosin contractions. Together, these lead to oscillating tension on the mechanosensitive adaptor protein talin on substrates with a stiffness of healthy adult heart tissue, compared with no tension on embryonic heart stiffness and continuous stretching on fibrotic stiffness. Moreover, we show that activation of PKC leads to the induction of cardiomyocyte hypertrophy in a stiffness-dependent way, through activation of non-muscle myosin. Finally, PKC and non-muscle myosin are upregulated at the costameres in heart disease, indicating aberrant mechanosensing as a contributing factor to long-term remodeling and heart failure. Graphical Abstract Highlights • Talin in cardiomyocytes is unstretched, cyclically stretched, or continuously stretched • Talin stretching depends on stiffness, myofibrillar tension, and non-myofibrillar tension • Non-myofibrillar contractility requires PKC, Src, FHOD1, and non-muscle myosin • PKC and non-muscle myosin activity are enhanced in cardiac disease Pandey et al. identify that cardiomyocytes sense the rigidity of the heart by measuring the combined forces from non-muscle and muscle myosin. This can result in cyclic or continuous stretching of the mechanosensitive protein talin, depending on the substrate stiffness and the level of non-muscle myosin activity. |
| Databáze: | OpenAIRE |
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