Chapter

Cardiac Cytoarchitecture

pp 15-39

Date:

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

  • Meghan B. KnightAffiliated withCardiovascular Modeling Laboratory, University of California, Irvine
  • , Anna GrosbergAffiliated withCardiovascular Modeling Laboratory, University of California, Irvine Email author 
  • , Megan L. McCainAffiliated withDepartment of Biomedical Engineering, University of Southern California Email author 

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Abstract

The heart is a dynamic, electrically activated, chemically sensitive, mechanical pump with a regular rhythm that must operate without interruption for decades. The function of the heart is an emergent property of highly organized structures that span multiple spatial scales (Fig. 2.1). On the organ level, the heart is divided into four chambers. Two of these chambers, the ventricles, are thick-walled muscular chambers that are particularly constructed to work as pressure pumps and contract in a twisting manner to efficiently squeeze blood from the chamber. The walls of the ventricle comprise layers of two-dimensional sheets of laminar cardiac tissue. The tissue itself consists of highly aligned, elongated, cylindrical cardiac myocytes. Cardiac myocytes are spanned by parallel bundles of myofibrils, which consist of repeating sarcomere units. Sarcomeres are nanoscale structures composed of thick myosin filaments and thin actin filaments that slide past each other and shorten the sarcomere in response to an action potential. Because all sarcomeres within a cell are aligned, and all cells in a tissue are aligned, the amount of uniaxial force generated by the tissue as a whole is maximized due to its multi-scale organization. To achieve synchronous contraction, myocytes couple together via specialized cell–cell junctions, known as intercalated discs, which provide both mechanical adhesion and rapid electrical communication. Thus, the pumping function of the heart, which is multiple centimeters in diameter, is dependent on spatial organization that spans all the way down to the nanoscale. In this chapter, we will describe the role of the structure of single cardiac myocytes, cell–cell junctions, and multicellular tissues in the function of the healthy heart and how these structure–function relationships become disrupted in disease. We will focus on studies that have used in vitro tools to mimic different architectures observed in developing, healthy, and diseased hearts and make functional readouts in a controlled setting.
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Fig. 2.1

The multi-scale structure of the heart. The function of the heart is dependent on its hierarchical architecture, which spans organ, tissue, cellular, and molecular levels