In Vitro Tools for Quantifying Structure–Function Relationships in Cardiac Myocyte Cells and Tissues

Quantitative Evaluation of Cardiac Cell Interactions and Responses to Cyclic Strain

“…In this work, we investigated cardiac tissue reorganization by examining co-cultures of the two dominant cell types in the myocardium, fibroblasts, and cardiomyocytes under the influence of cyclic strain to model both the cellular composition of the heart in health and pathology as well as the cardiac mechanical environment (Table 2) [1][2][3]. In order to measure the cell type-specific organization, we developed an image-processing pipeline to automatically classify images of tissues stained with α-actinin and to use the classification labels to separate the actin belonging to fibroblasts and striated myocytes (Figure 1).…”

“…The two dominant cell types in the myocardium are cardiomyocytes and cardiac fibroblasts; cardiomyocytes generate contractile force [1][2][3], while fibroblasts play vital roles in maintaining functions within the heart, such as extracellular matrix production, cardiac remodeling, cell-cell signaling, promoting blood vessel formation, and secretion of growth factors and cytokines [4][5][6]. In a healthy heart, cardiomyocytes and fibroblasts are organized along the direction of contraction [7][8][9].…”

“…To communicate, the cardiac cells are electrically and mechanically coupled via gap and adherens junctions, both heterogeneously (i.e., cardiomyocyte-fibroblast) and homogeneously (i.e., cardiomyocytecardiomyocyte and fibroblast-fibroblast) [33]. The most abundant gap and adherens junctions in the heart are connexin 40 (Cx40), connexin 43 (Cx43), and connexin 45 (Cx45), and N-cadherin (N-cad) [1,6,26,[33][34][35][36][37]. Interestingly, by inhibiting or blocking a subset of these junctions, studies have shown inhibited cell-cell contact, adhesion, and signaling between cells [1,26,33,36,[38][39][40][41].…”

“…The most abundant gap and adherens junctions in the heart are connexin 40 (Cx40), connexin 43 (Cx43), and connexin 45 (Cx45), and N-cadherin (N-cad) [1,6,26,[33][34][35][36][37]. Interestingly, by inhibiting or blocking a subset of these junctions, studies have shown inhibited cell-cell contact, adhesion, and signaling between cells [1,26,33,36,[38][39][40][41]. Therefore, observing interactions between distinct cardiac cell types in confluent co-cultures through intercellular junctions or physical contact may be necessary to understand the guiding mechanisms for cardiac tissue reorganization in its native dynamic mechanical environment.…”

Striated myocyte structural integrity: Automated analysis of sarcomeric z-discs

“…It has been used to characterize the developmental stage [1][2][3], engineered tissues [4][5][6][7][8], effects of disease [9][10][11][12] or injury [13][14][15][16], and treatment with pharmacological agents [17] as well as used to predict function [18][19][20]. Indeed, the ability of striated muscle cells to contract is dependent on the nearly crystalline order of its cytoskeletal components [21,22], which makes evaluation of structure paramount. Skeletal and cardiac myocytes are composed of parallel myofibrils, which are spanned by repeating sarcomere units that produce a contractile force parallel to the thick myosin filaments as they slide past the thin actin filaments [23,24].…”