Development of Magnetic Torque Stimulation (MTS) Utilizing Rotating Uniform Magnetic Field for Mechanical Activation of Cardiac Cells

Abstract

Regulation of cell signaling through physical stimulation is an emerging topic in biomedicine. Background: While recent advances in biophysical technologies show capabilities for spatiotemporal stimulation, interfacing those tools with biological systems for intact signal transfer and noncontact stimulation remains challenging. Here, we describe the use of a magnetic torque stimulation (MTS) system combined with engineered magnetic particles to apply forces on the surface of individual cells. MTS utilizes an externally rotating magnetic field to induce a spin on magnetic particles and generate torsional force to stimulate mechanotransduction pathways in two types of human heart cells—cardiomyocytes and cardiac fibroblasts. Methods: The MTS system operates in a noncontact mode with two magnets separated (60 mm) from each other and generates a torque of up to 15 pN µm across the entire area of a 35-mm cell culture dish. The MTS system can mechanically stimulate both types of human heart cells, inducing maturation and hypertrophy. Results: Our findings show that application of the MTS system under hypoxic conditions induces not only nuclear localization of mechanoresponsive YAP proteins in human heart cells but also overexpression of hypertrophy markers, including β-myosin heavy chain (βMHC), cardiotrophin-1 (CT-1), microRNA-21 (miR-21), and transforming growth factor beta-1 (TGFβ-1). Conclusions: These results have important implications for the applicability of the MTS system to diverse in vitro studies that require remote and noninvasive mechanical regulation.

Biomaterials Tailoring at the Nanoscale for Tissue Engineering and Advanced Therapies

“…Another strategy to physically stimulate biological processes encompasses the use of magnetic nanoparticles. Song and colleagues combined a magnetic torque stimulation system with lectin surface functionalized magnetic particles, resulting in the possibility to apply forces on the surface of cells operating in a noncontact mode [ 10 ]. The developed systems turned out to be able to stimulate both cardiomyocytes and cardiac fibroblasts and induce the upregulation of hypertrophic markers in hypoxic cardiomyocytes.…”