Conditions leading to myocardial dysfunction and heart failure often have mechanical origins. Myocardial infarction and heart failure are characterized by maladaptive remodeling of the cardiac tissue wall and are often accompanied by diffuse fibrosis. At the cellular level, changes in shape (aspect ratio) are seen in a number of clinical conditions associated with various forms of cardiomyopathy. The overarching hypothesis is that remodeling and reorganization of the myocyte-cytoskeletal (CSK) architecture is a collective (structurally integrative) process, requiring instructive extracellular signals (e.g., cell-ECM and cell-cell contact). Damaged tissue cannot provide the requisite mechanical microenvironment (e.g., anisotropic) dependent cues
The intracellular architecture plays a critical role in transducing mechanical signals into biochemical processes responsible for regulating cell function. Mechanical control of the microenvironment (structural anisotropy, topography) provides both the cues and means for affecting cell fate (see Figure). This mechanobiological perspective forms the basis for viewing the heart (tissue) as a mechanotransducing anisotropic continuum, exhibiting constant mechanosensory-driven self-recurrent adjustment of the cytoskeleton through a tight interplay between its force generation activity and concurrent architecture (sarcomerogenesis / myofibrillogenesis). It is becoming increasingly clear that changes in cardiac function accompanying tissue remodeling associated with heart failure are brought about by the disruption of the mechanotransduction continuum (e.g., disorganized cells alignment and altered cell phenotype). The ability to surgically engineer (reverse remodel) the mechanical milieu of cells provides a compelling rationale for advancing novel biomaterial-based therapeutic strategies (e.g. injectable scaffolds).
A – Fibronectin-microprinted adhesive patterns (‘mechano-alphabet’), representing the spectrum of the anisotropic and isotropic adhesion imposed conditions (top) and corresponding myocyte cytoskeleton (CSK) architectural features (bottom). B – Polarity of myofibrils (MFs) induced by the anisotropic adhesion feature (arrows) follows the tensile field (crossbow). Myocytes demonstrate the continual MF formation, revealing the spatial integrity of CSK even over the non-adhesive zones. Stress-fibers in the fibroblast are localized at the cell edges and demonstrate their longitudinal integrity.
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