Measuring Single Cardiac Myocyte Contractile Force via Moving a Magnetic Bead

Abstract

One of the biggest problems of heart failure is the heart's inability to effectively pump blood to meet the body's demands, which may be caused by disease-induced alterations in contraction properties (such as contractile force and Young's modulus). Thus, it is very important to measure contractile properties at single cardiac myocyte level that can lay the foundation for quantitatively understanding the mechanism of heart failure and understanding molecular alterations in diseased heart cells. In this article, we report a novel single cardiac myocyte contractile force measurement technique based on moving a magnetic bead. The measuring system is mainly composed of 1), a high-power inverted microscope with video output and edge detection; and 2), a moving magnetic bead based magnetic force loading module. The main measurement procedures are as follows: 1), record maximal displacement of single cardiac myocyte during contraction; 2), attach a magnetic bead on one end of the myocyte that will move with myocyte during the contraction; 3), repeat step 1 and record contraction processes under different magnitudes of magnetic force loading by adjusting the magnetic field applied on the magnetic bead; and 4), derive the myocyte contractile force base on the maximal displacement of cell contraction and magnetic loading force. The major advantages of this unique approach are: 1), measuring the force without direct connections to the cell specimen (i.e., "remote sensing", a noninvasive/minimally invasive approach); 2), high sensitivity and large dynamic range (force measurement range: from pico Newton to micro Newton); 3), a convenient and cost-effective approach; and 4), more importantly, it can be used to study the contractile properties of heart cells under different levels of external loading forces by adjusting the magnitude of applied magnetic field, which is very important for studying disease induced alterations in contraction properties. Experimental results demonstrated the feasibility of proposed approach.

Four Dimensional (4-D) BioChemInfoPhysics Models of Cardiac Cellular and Sub-Cellular Vibrations (Oscillations)

“…Model developments: Based on the published experimental results [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] , we approximately consider, BF in SR, cells or extra-cells, as quasi liquid plasmas in physics, the plasmas are quasi neutral electromagnetically; biological or biochemical components such as free Ca++ in BF, SR SubMembrane (SRSM) or Cell Membrane (CM), Ca++H+ (Ca++ or Na+K+) ATPases, NCX, Ca++ carriers and myosin heads, because disturbances, internal excitations or external stimulations always exist, often are displaced from their equilibrium positions or distances, the redistribution of charges and masses will respectively set up forces, tensions or pressures at the components. The forces, the tensions or the pressures will restore the components back to their original equilibrium positions or distances and could initiate a vibration (oscillation), even a resonance.…”

“…Scientists have studied the mechanisms for more than 100 years [2,3] and proposed models for the mechanisms. The models respectively involved mathematics [4,5] , biophysics [6,7] , biochemistry [8][9][10][11][12][13][14][15][16][17][18] . But, none involved the automation of the vibrations (oscillations) [2] .…”

“…In this investigation, based on published data or results [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] , conservation laws of the momentum as well as the energy, in views of biology, biochemistry, informatics and physics (BioChemInfoPhysics), we proposed models of cardiac cellular and sub-cellular vibrations (oscillations) of biological components, such as free ions in Biological Fluids (BF), Biological Membranes (BM), Ca++H+ (Ca++ and Na+K+) ATPases, Na+Ca++ exchangers (NCX), Ca++ carriers and myosin heads. Moreover, we discuss our models' general applications and general meanings in biology.…”

Dynamic Model for Characterizing Contractile Behaviors and Mechanical Properties of a Cardiomyocyte

“…Some heart diseases that can damage the normal contraction and relaxation behavior of heart cells, even in the early stages (2), may result from differences in contractile forces and mechanical properties between healthy and diseased cells. Therefore, analyzing the contractile force, mechanical properties, and dynamic beating behavior of heart cells is of great significance for the quantitative understanding of the mechanism of heart disease and the molecular alterations that occur in diseased heart cells (3). Moreover, cardiomyocytes have been used as actuators in the development of bio-syncretic robots in recent years (4)(5)(6)(7)(8)(9) for their advantageous functional features, including spontaneous contraction, high energy conversion efficiency, and high energy density (10).…”

“…The stretching method is the most direct measuring approach. This method is implemented by holding onto both ends of a cell with microclamps, beads, or hooks, and then measuring the contractility of the living beating cell (3,24,25). Another simple method is to use a micrometer-scale, elastic pillar array as a substrate to culture heart cells.…”