Contractile tension and beating rates of self-exciting monolayers and 3D-tissue constructs of neonatal rat cardiomyocytes

Abstract

The CellDrum technology (The term 'CellDrum technology' includes a couple of slightly different technological setups for measuring lateral mechanical tension in various types of cell monolayers or 3D-tissue constructs) was designed to quantify the contraction rate and mechanical tension of self-exciting cardiac myocytes. Cells were grown either within flexible, circular collagen gels or as monolayer on top of respective 1-mum thin silicone membranes. Membrane and cells were bulged outwards by air pressure. This biaxial strain distribution is rather similar the beating, blood-filled heart. The setup allowed presetting the mechanical residual stress level externally by adjusting the centre deflection, thus, mimicking hypertension in vitro. Tension was measured as oscillating differential pressure change between chamber and environment. A 0.5-mm thick collagen-cardiac myocyte tissue construct induced after 2 days of culturing (initial cell density 2 x 10(4) cells/ml), a mechanical tension of 1.62 +/- 0.17 microN/mm(2). Mechanical load is an important growth regulator in the developing heart, and the orientation and alignment of cardiomyocytes is stress sensitive. Therefore, it was necessary to develop the CellDrum technology with its biaxial stress-strain distribution and defined mechanical boundary conditions. Cells were exposed to strain in two directions, radially and circumferentially, which is similar to biaxial loading in real heart tissues. Thus, from a biomechanical point of view, the system is preferable to previous setups based on uniaxial stretching.

Mechano-Pharmacological Characterization of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells

“…The herein and in other papers [31,34] presented experimental results provide a fundamental basis for the validation and parameterization of the computational model previously presented in [42] where theoretical details and the simulation results in Fig. 7 and Fig.…”

“…Previously, this technology has been applied to neonatal rat cardiac myocytes [31] and endothelial cells [32].…”

Muscle on a chip: In vitro contractility assays for smooth and striated muscle

“…However, most “lab on a chip” contractility assays are based on single cells within microfluidic channels (Cheng, Klauke, Sedgwick, Smith, & Cooper, 2006; Cheng, Klauke, Smith, & Cooper, 2010; Tan, et al, 2003; Werdich, et al, 2004; Zhao, Lim, Sawyer, Liao, & Zhang, 2007), which do not always reproduce multi-cellular pharmacological responses (Kaneko, Kojima, & Yasuda, 2007). Various tissue contractility assays (Kim, et al, 2008; Linder, et al, 2010; Park, et al, 2005) are difficult to translate to higher throughput systems with controlled cellular microenvironments. Impedance measurements of contracting myocyte monolayers within multi-well plates is another in vitro approach (Guo, et al, 2011).…”

A 3d Electromechanical Fem-Based Model for Cardiac Tissue

“…For thin cardiac tissue constructs these tasks have been addressed with a device called CellDrum [24,25]. The CellDrum is a circular, 4 μm thin silicone membrane with a diameter of 16 mm.…”