Publication date: 25th July 2016
The complex architecture of cardiac extracellular matrix (ECM) provides a unique 3D environment for cardiomyocytes to exert their contractile function in physiological conditions. The derangement of ECM integrity occurring during the onset and progression of cardiac diseases drives a modification in the nanotopography and mechano-physical properties of the ECM itself, thus impairing cardiac cell contractility and organ function. Our group demonstrated that slight dynamic modifications in substrate mechanics and nanotopography affects cardiac cell maturation and function and that cell response to such conditions is mediated by their mechanosensing apparatus. Additionally, immunohistochemistry analysis of infarcted mouse hearts and cardiac biopsies obtained from human donors and cardiac patients confirms that the dramatic structural changes occurring as a consequence of myocardial infarction (MI) and during the progression of cardiac pathology towards heart failure causes a switch in cardiac cell mechanosome. Cardiac decellularized tissues obtained from physiological and pathological conditions feature the three dimensional cues, mechanical properties, chemical complexity and the native organization of heart tissue in health and disease and thus are here proposed as models to: 1) set up in vitro tools to investigate the molecular determinants of cell-ECM interaction in cardiac tissue; 2) disclose the possible contribution of cell mechanosensors to cardiac pathologies. In this study, we demonstrate that second harmonic generation imaging and scanning electron microscopy can be implemented to obtain high-resolution 3D maps of cardiac dECM nanotopography. Furthermore, preliminary cell-dECM interaction experiments suggested that physiological and pathological conditions can be reproduced in vitro by these tools. Altogether our data show that cardiac dECMs are powerful and reliable toolboxes to monitor cardiac nanostructure changes and to investigate cardiac system mechanobiology.
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