Micromechanical regulation in cardiac myocytes and fibroblasts: implications for tissue remodeling

Abstract

Cells of the myocardium are at home in one of the most mechanically dynamic environments in the body. At the cellular level, pulsatile stimuli of chamber filling and emptying are experienced as cyclic strains (relative deformation) and stresses (force per unit area). The intrinsic characteristics of tension-generating myocytes and fibroblasts thus have a continuous mechanical interplay with their extrinsic surroundings. This review explores the ways that the micromechanics at the scale of single cardiac myocytes and fibroblasts have been measured, modeled, and recapitulated in vitro in the context of adaptation. Both types of cardiac cells respond to externally applied strain, and many of the intracellular mechanosensing pathways have been identified with the careful manipulation of experimental variables. In addition to strain, the extent of loading in myocytes and fibroblasts is also regulated by cues from the microenvironment such as substrate surface chemistry, stiffness, and topography. Combinations of these structural cues in 3D are needed to mimic the micromechanical complexity derived from the extracellular matrix of the developing, healthy, or pathophysiologic heart. An understanding of cardiac cell micromechanics can therefore inform the design and composition of tissue engineering scaffolds or stem cell niches for future applications in regenerative medicine.

Comparative proteomic assessment of matrisome enrichment methodologies

“…The heart is composed of myocardial muscle and collagenous heart valves and because of the periodic contractions of the myocardium, there are high demands for tissue flexibility and contractility [27]. The ECM in the heart is necessary for the distribution of mechanical forces throughout the myocardium and transmission of electromechanical signals maintaining systolic and diastolic function [28,29].…”

Orientation-specific responses to sustained uniaxial stretching in focal adhesion growth and turnover

“…Cells within these tissues are mechanosensitive, responding to these mechanical inputs by changing ion channel configurations (1-3), cytoskeleton organization (4-6), mRNA splicing (7), gene expression (8)(9)(10), and posttranslational protein modification (11)(12)(13). Although many forms of mechanical stimuli occur physiologically, the most well studied are the responses of cells to cyclic stretch to specifically simulate the contraction/relaxation cycles that occur within the cardiovascular and pulmonary systems (14)(15)(16)(17). However, sustained stretch also commonly occurs in tissues-e.g., when injury-induced swelling causes local hydrostatic pressure increase (18), in long-term blood pressure increase (16,19), during prolonged muscle contraction (20,21), or when the bladder retains large volume of urine (22,23).…”

Extracellular matrix-mediated cellular communication in the heart

“…The ECM is also essential for efficient cardiac function via myocyte alignment, regulation of blood flow during contraction, compliance and maintenance of appropriate tissue tensile modulus. Therefore, the ECM is crucial to maintain appropriate cardiac integrity and pump function [35]. Conversely, disruption of ECM homeostasis is a central factor for cardiac dysfunction, pathologic remodeling and fibrosis following cardiac injury [3].…”