Automated Dual-Mode Cell Monitoring To Simultaneously Explore Calcium Dynamics and Contraction-Relaxation Kinetics...

Area of Science:

• Cardiology
• Biophysics
• Cell Biology

Background:

• Cardiomyocyte contractility relies on intricate calcium dynamics.
• Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are valuable models for cardiac research.
• Existing imaging techniques often lack the capability to simultaneously assess calcium signaling and mechanical function.

Purpose of the Study:

• To develop and validate a novel dual-mode cell imaging system.
• To simultaneously measure intracellular calcium and cardiomyocyte contractility.
• To investigate the relationship between calcium dynamics and contraction-relaxation kinetics in hiPSC-CMs.

Main Methods:

• Digital holographic microscopy for quantitative phase imaging (contractility).
• Live cell calcium imaging.
• Automated image analysis for simultaneous data acquisition.
• Application of pharmacological agents (isoprenaline, E-4031) to modulate calcium dynamics.

Main Results:

• Simultaneous measurement of intracellular calcium and dry mass redistribution (contractility) was achieved.
• Pharmacological interventions demonstrated distinct phases of calcium regulation.
• An early phase of calcium regulation influences relaxation, while a late phase affects beat frequency.

Conclusions:

• The dual-mode imaging system effectively links calcium dynamics to cardiomyocyte contractility.
• Calcium regulation in cardiomyocytes comprises at least two distinct phases with differential effects.
• This technique holds promise for drug discovery and personalized medicine in cardiology.