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.
Highlights
Mechanical force and its use in mediating molecular functions, cell signaling, and behavioral responses are pivotal in the regulation of complex biological systems [1,2,3,4]
Since a permanent magnet made of neodymium is the strongest one in the market and too short distance between the magnets impairs the uniformity of magnetic field in the working area, the magnetic field strength of ~200 mT and its corresponding torque were almost the maximums we could obtain
These results suggest that the magnetic torque stimulation (MTS) system can cover a 35-mm-diameter circular region depending on the magnet configuration, providing the possibility of highly parallel yet uniform mechanical stimulation of many cells simultaneously
Summary
Mechanical force and its use in mediating molecular functions, cell signaling, and behavioral responses are pivotal in the regulation of complex biological systems [1,2,3,4]. While the rapid progress in the development of force stimulation systems has improved the understanding of mechanotransduction processes [7,8,9], the use of these systems in various applications is currently challenging due to their short working distances and/or contact-requiring modes of action [10,11]. Application of these systems is necessary to facilitate laboratory investigations of in vitro systems and to develop translational research for health technology innovations [10,11,12]. This observation implies that the capability for long-distance and multiple stimulations would augment the intrinsic merits of magnetic systems as candidates for noninvasive mechanical stimulation systems [22]
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