Cardiomyocytes sense matrix rigidity through a combination of muscle and non-muscle myosin contractions
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Mechanical properties are cues for many biological processes in health or disease. In the heart, changes to the extracellular matrix composition and cross-linking results in stiffening of the cellular microenvironment during development. Moreover, myocardial infarction and cardiomyopathies lead to fibrosis and a stiffer environment, affecting cardiomyocyte behaviour. Here we identify that single cardiomyocyte adhesions sense simultaneous (fast oscillating) cardiac and (slow) non-muscle myosin contractions. Together this leads to oscillating tension on the mechanosensitive adaptor protein talin on substrates with a stiffness of healthy adult heart tissue, compared to 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 contributing factor to long term remodelling and heart failure.