Following a cardiovascular event (ischemic insult, long term exposure to pressure or volume overload), cardiac matrix is degraded and substituted by a scar, having a different nanostructure and compliance ( Spinale, 2007). The best example of how pathology-driven changes in ECM mechanics and architecture impact on tissue and organ function is cardiac remodeling. Finally, we give few paradigmatic examples highlighting the emerging role of malfunctions in cell mechanosensing apparatus in the onset and progression of pathologies. Specifically, by recapitulating the processes involved in the interpretation of ECM remodeling by Focal Adhesions at cell-matrix interphase, we revise the role of cytoskeleton tension as the second messenger of the mechanotransduction process and the action of mechano-responsive shuttling proteins converging on stage and cell-specific transcription factors. Here we provide a critical review of the recent insights into the molecular basis of cellular mechanotransduction, by analyzing how mechanical stimuli get transformed into a given biological response through the activation of a peculiar genetic program. Only lately, though, the importance of mechanical cues in controlling cell function (e.g., proliferation, differentiation, migration) has been acknowledged. As such, these changes occur regularly during tissue development and are a hallmark of the pathologies of aging.

Local changes in ECM composition and mechanics are driven by a feed forward interplay between the cell and the matrix itself, with the first depositing ECM proteins that in turn will impact on the surrounding cells. The intracellular molecular processes through which such physical cues are transformed into a biological response are collectively dubbed as mechanotransduction and are of fundamental importance to help the cell timely adapt to the continuous dynamic modifications of the microenvironment. Living cells are constantly exposed to mechanical stimuli arising from the surrounding extracellular matrix (ECM) or from neighboring cells. 4Department of Biomaterials Science, Institute of Dentistry, University of Turku, Turku, Finland.3Competence Center for Mechanobiology in Regenerative Medicine, INTERREG ATCZ133, Brno, Czechia.2Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czechia.Anne’s University Hospital, Brno, Czechia 1Center for Translational Medicine, International Clinical Research Center, St.

Perestrelo 1, Vladimír Vinarský 1,3, Stefania Pagliari 1 and Giancarlo Forte 1,3,4*

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