Tools for studying and modulating (cardiac muscle) cell mechanics and mechanosensing across the scales

Abstract

Cardiomyocytes generate force for the contraction of the heart to pump blood into the lungs and body. At the same time, they are exquisitely tuned to the mechanical environment and react to e.g. changes in cell and extracellular matrix stiffness or altered stretching due to reduced ejection fraction in heart disease, by adapting their cytoskeleton, force generation and cell mechanics. Both mechanical sensing and cell mechanical adaptations are multiscale processes. Receptor interactions with the extracellular matrix at the nanoscale will lead to clustering of receptors and modification of the cytoskeleton. This in turn alters mechanosensing, force generation, cell and nuclear stiffness and viscoelasticity at the microscale. Further, this affects cell shape, orientation, maturation and tissue integration at the microscale to macroscale. A variety of tools have been developed and adapted to measure cardiomyocyte receptor-ligand interactions and forces or mechanics at the different ranges, resulting in a wealth of new information about cardiomyocyte mechanobiology. Here, we take stock at the different tools for exploring cardiomyocyte mechanosensing and cell mechanics at the different scales from the nanoscale to microscale and macroscale.

Real-Time Quantification of Cell Mechanics and Functions by Double Resonator Piezoelectric Cytometry — Theory and Study of Cellular Adhesion of HUVECs

“…The applicability of equations (3,4) and (15,16) to both AT and BT cut crystals was experimentally verified in both Newtonian sucrose solutions and non-Newtonian (viscoelastic) PEG 2000 solutions at different concentrations (Figure S1). with the largest storage and loss moduli, obeying the cellular tensegrity model.…”

“…The Sauerbery equation 1 and the above theoretical relations between the measured changes in frequency, motional resistance or bandwidth and the liquid's viscosity, viscoelasticity were derived for AT-cut quartz crystals, however, it was theoretically predicted that equations ( 1) and ( 3) can be extended to other pure shear mode cuts including BT-cut but with some different response slopes owing to their difference in shear modulus, [18] shear wave velocity or acoustic impedance. Here we further assume that equations (4)(5)(6) can also be applied to other pure shear mode cuts including BT-cut.…”

“…For some cellular functions, mechanical changes accompany with the biological processes which can be used directly to characterize these functions, e.g., mechanical contraction and relaxation cycles of beating cardiomyocytes, [1] single and collective cell migrations, [2] different phases of cellular adhesion. [3] These physiological functions have important implications in assessing pathological status of major cardiovascular and cancer diseases; [4,5] and drug development and assessments. [6] Mechanical forces affect other cellular functions including proliferation and differentiation which may take days to have functional changes, whereas direct force transmission normally occurs on much short scale of milliseconds to seconds, followed by biochemical signaling in minutes, and cellular responses such as gene expression in hours.…”

Pressure and stiffness sensing together regulate vascular smooth muscle cell phenotype switching

“…Arteries are composite structures, with mechanical properties that differ between micro-and macroscale, and direction of strain. Generally, microscale stiffnesses are magnitudes lower compared to the macroscale (23,24), which is a result of the specific mechanical behavior at different length scales, as well as sample preparation and measurement techniques (25). At the microscale, comparative studies between the individual arterial wall layers suggested that the intima was more compliant compared to the media layer (26) and studies report values that ranged from 5 to 50 kPa (26,27) and ~30 to 190 kPa (28)(29)(30) in the intima and media layers, respectively.…”

Simultaneous assessment of radial and axial myocyte mechanics by combining atomic force microscopy and carbon fibre techniques

“…Cellular and subcellular mechanics can be studied using optical tweezers [16][17][18]. The various techniques used to probe cell mechanics have been reviewed in detail elsewhere [19,20]. In spite of this wide range of tools, simultaneous measurements of passive and active single cardiomyocyte mechanics in axial and radial directions have not been reported.…”