Cardiac Action Potentials

BMSEED's physiological cell stretcher (MEASSuRE-Mini) and flexible and stretchable microelectrode arrays (sMEAs) offer innovative solutions for cardiac classification and analysis. These advanced tools enable researchers to study cardiac action potentials and distinguish between different cardiac subtypes.

Basic cardiac action potential

Cardiac Action Potential Analysis

The cardiac action potential is a crucial indicator of cardiac cell subtypes, consisting of distinct phases: depolarization, plateau, and repolarization. The duration and kinetics of these phases help determine whether a cell behaves like an atrial, nodal, or ventricular cell.

.Atrial Cardiomyocytes:

  • Minimal plateau phase

  • Linear repolarization

  • Shorter duration

  • Triangular shape

Ventricular Cardiomyocytes:

  • Pronounced plateau phase

  • Longer duration

  • Square shape

Why Cardiac Classification Matters: Understanding and classifying cardiac action potentials is critical for advancing cardiovascular research, drug screening, and personalized medicine. Accurate classification of arrhythmias, electrophysiological patterns, and tissue responses allows researchers and clinicians to detect abnormalities, predict drug efficacy, and design targeted therapies.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) on BMSEED’s stretchable MEA; A. Patino Ph.D., Arizona State University

Physiological Stretching of Cardiomyocytes

Cardiac cells, or cardiomyocytes, experience continuous mechanical stretching due to the rhythmic contractions of the heart. Replicating these physiological strain conditions in vitro is essential for cardiac research, as it enables the study of cellular responses to mechanical stimuli, investigation of cardiac diseases, and development of therapeutic interventions.

In vivo, cardiomyocytes undergo cyclic stretching with relatively low strain rates and magnitudes. This mechanical environment is crucial for maintaining their structural integrity and function. To simulate these conditions in vitro, a cell stretcher can be used to provide:

  • Low Strain Rates: Cardiac cells typically experience strain rates that are significantly lower compared to those encountered during pathological conditions. Accurately replicating these low strain rates is vital for physiological relevance.

  • Controlled Strain Magnitudes: The ability to apply precise and consistent strain magnitudes ensures that the mechanical environment of cardiomyocytes closely mirrors that of the native cardiac tissue.

  • Electrophysiological Stimulation and Recording: Measure the health, function, and maturity of cardiac cells before and after stretching. Monitor cardiac action potentials over long-term, chronic experiments inside of an incubator.

MEASSuRE Mini (BMSEED’s Physiological Cell Stretcher)

MEASSuRE-Mini: A Physiological Cell Stretcher

BMSEED's MEASSuRE-Mini system is a model of MEASSuRE designed to address the limitations of traditional in vitro physiological models by integrating:

  • Enhanced Stretching Mechanisms: MEASSuRE allows for precise and varied stretching profiles, closely mimicking the diverse mechanical forces experienced by cells in vivo. This includes the ability to simulate different types of mechanical stress, such as cyclic stretch, which is crucial for studying dynamic biological processes.

  • Electrophysiology Integration: The system combines mechanical stretching with electrophysiological measurements, enabling simultaneous assessment of cellular electrical activity and mechanical responses, such as cardiac action potentials.

  • Imaging Capabilities: MEASSuRE incorporates an imaging module that allow for real-time visualization of cellular and subcellular structures during mechanical stimulation, facilitating comprehensive analysis of cellular responses.

Cardiomyocytes - An Overview (from ScienceDirect)

Applications in Cardiac Research

Utilizing the MEASSuRE-Mini physiological cell stretcher in cardiac research offers several advantages:

  • Modeling Cardiac Mechanics: Researchers can replicate the mechanical environment of the heart, enabling the study of mechanotransduction pathways and their role in cardiac function and disease.

  • Drug Testing and Development: The system allows for the evaluation of pharmacological agents under conditions that closely resemble the in vivo cardiac environment, improving the predictive value of in vitro studies.

  • Tissue Engineering: MEASSuRE can be used to condition engineered cardiac tissues, promoting the development of functional tissue constructs for regenerative medicine applications.

By providing a platform that accurately replicates the physiological stretching conditions of cardiac cells, the MEASSuRE system enhances the relevance and applicability of in vitro cardiac research, bridging the gap between laboratory findings and clinical outcomes.

Traditional rigid MEAs often fall short when interfacing with dynamic and mechanically active cardiac tissues. BMSEED's stretchable MEAs are engineered to overcome these limitations by offering:

  • Flexibility: Conform to the natural curvature and movement of cardiac tissues.

  • High-Resolution Recording: Capture subtle electrical signals with precision for accurate classification.

  • Long-Term Stability: Maintain signal integrity over extended periods, enabling chronic studies.

  • Biocompatibility: Minimize tissue damage and immune response during long-term integration.

Advantages of BMSEED's Stretchable MEAs

BMSEED's sMEAs offer unique benefits for cardiac classification:

  • Soft, Flexible Substrate: Allows cells to grow naturally, mimicking the dynamic environment of cardiac tissue.

  • High Strain Capacity: Up to 50% strain at 80-90/s, enabling the study of mechanotransduction in cardiac cells.

  • Real-time Recording and Stimulation: Facilitates the analysis of extracellular electrophysiological activity in various experimental setups.

  • Compatibility: Works seamlessly with Multi Channel Systems data acquisition systems.

BMSEED's sMEAs enable researchers to:

  • Measure action potential morphology without patch clamp techniques.

  • Quantify rise time, cardiac action potential duration, beat period, and triangulation.

  • Study intact cardiomyocyte syncytium.

  • Investigate the effects of mechanical stress on cardiac cell behavior.

By utilizing BMSEED's stretchable MEAs, researchers can gain valuable insights into cardiac cell subtypes and their electrophysiological properties, advancing our understanding of heart function and disease mechanisms.

Frequently Asked Questions About Cardiac Applications

1. In what ways can MEASSuRE be used to study cardiac cells and function?

The MEASSuRE Physiological Cell Stretcher, paired with BMSEED’s stretchable microelectrode arrays (sMEAs), is a powerful tool for advancing cardiac research. It enables researchers to investigate various cardiac phenomena by accurately replicating the heart's mechanical and electrical environment. Key applications include:

  • Arrhythmia Detection: Classify and differentiate arrhythmic events with high temporal and spatial resolution.

  • Drug Screening: Evaluate the real-time effects of drug compounds on cardiac tissue electrophysiology.

  • Cardiotoxicity Assessment: Identify potential cardiotoxic effects of pharmaceutical compounds early in the drug development process.

  • Disease Modeling: Study genetic and acquired cardiac diseases using both 2D monolayer cultures and 3D tissue-engineered models.

Seamless Integration with Cardiac Models:
MEASSuRE integrates smoothly with 2D and 3D cardiac models, allowing researchers to explore cardiac activity from single-cell action potentials to complex tissue-level responses.

Accelerating Drug Discovery:
Cardiovascular safety concerns are a leading cause of drug attrition during preclinical and clinical trials. MEASSuRE helps pharmaceutical researchers:

  • Detect early signs of cardiotoxicity.

  • Optimize lead compounds for cardiac safety.

  • Reduce dependence on animal models, streamlining the drug development pipeline.

By combining mechanical stretching with real-time electrophysiological monitoring, MEASSuRE offers a comprehensive solution for cardiac research, disease modeling, and safer drug development.

2. What advantages does using the MEASSuRE system offer for cardiac research compared to traditional methods?

The MEASSuRE Physiological Cell Stretcher offers significant advantages for cardiac research by providing a more physiologically relevant platform compared to traditional in vitro methods.

Physiologically Relevant Mechanical Stimulation:
MEASSuRE accurately replicates the low strain rates and cyclic stretching that cardiomyocytes experience in the heart, enabling realistic modeling of both healthy and diseased cardiac conditions. Customizable strain profiles allow researchers to simulate conditions like hypertrophic cardiomyopathy or heart failure.

Advanced Disease Modeling and Mechanobiology Research:
The system facilitates in-depth studies on how mechanical forces influence cardiac disease progression, helping uncover mechanotransduction pathways involved in heart remodeling and dysfunction.

Integration with Electrophysiology and Imaging Tools:
MEASSuRE seamlessly integrates with stretchable microelectrode arrays (sMEAs) for real-time monitoring of cardiac action potentials during mechanical stimulation, aiding arrhythmia and drug response studies. It also supports live cell imaging, allowing detailed observation of cell behavior under stress.

Enhanced Drug Testing and Cardiotoxicity Screening:
By mimicking the heart's mechanical environment, MEASSuRE provides more predictive data for drug efficacy and safety, enabling early detection of cardiotoxic effects and reducing reliance on animal models.

Versatility with 2D and 3D Cardiac Models:
MEASSuRE is compatible with both 2D cardiomyocyte cultures and 3D engineered heart tissues, supporting studies from cardiac action potentials to complex tissue responses.

Scalable and Long-Term Research Capabilities:
Designed for long-term studies inside of an incubator and scalable for high-throughput drug screening, the MEASSuRE-Mini accelerates cardiac research and therapeutic development.

In summary, MEASSuRE’s precise mechanical stimulation, integration with advanced research tools, and versatility make it a powerful solution for advancing cardiac research and improving drug development.

  • Yes, MEASSuRE allows for customizable strain, strain rates, and strain profiles to model abnormal mechanical environments, aiding in the study of disease progression and treatment responses.

  • MEASSuRE is a cell stretcher that requires a flexible and stretchable membrane for cells to adhere to. BMSEED’s stretchable microelectrode arrays (sMEAs)provide a membrane that stretches with the cells made from biocompatible PDMS (polydimethylsiloxane).

    If electrophysiological measurements are not a requirement during cell stretching, a stretchable membrane without electrodes,BMSEED’s stretchwell (SW), can be used as a low-cost alternative to sMEAs.

    Finally, if cell stretching is not a requirement for your research, i.e. only electrophysiological measurements are required, traditional glass microelectrode arrays (gMEAs) can be used in addition to sMEAs and SWs.

  • Yes, MEASSuRE offers modular designs and customizable stretching programs to accommodate unique experimental requirements.

    Each module of MEASSuRE can be used as a standalone tool:

    • Electrophysiology Module: Low-cost, high performance data acquisition system for electrophysiology with up to 120-channels

    • Mechanics Module: Cell stretchers that are customized for specific applications, ranging from neurodegenerative diseases, neurotrauma, tissue engineering, to drug screening.

    • Cell Stretching and Imaging Module: Combined Mechanics Module for cell stretching and optical and/or fluorescence imaging to verify cell strain during stretching motion.

    Customizable strain, strain rates, and strain patterns are available with a single MEASSuRE system:

    • Strain: up to 20% (MEASSuRE-Mini) or up to 50% (MEASSuRE-Premium and MEASSuRE-X)

    • Strain Rate: up to 1/s (MEASSuRE-Mini), up to 50/s (MEASSuRE-Premium), or up to 90/s (MEASSuRE-X)

    • Strain Profile: radial (stretch in all directions), biaxial (stretch in two directions, perpendicularly), or uniaxial (stretch in one direction)

    Additional customizations can be requested.

  • Yes, MEASSuRE enables testing of cardiac drug efficacy and toxicity under physiologically relevant mechanical conditions, providing more predictive data than static cultures.

  • Stretchable microelectrode arrays (sMEAs) used with MEASSuRE help mature engineered cardiac tissues by applying mechanical conditioning that improves structural organization, contractility, and functionality.