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2 magnetic fields permit remote control of the cellular fate in the absence of chemical or biological agents. Often inspired by purported health hazards of environmental electromagnetic stray fields, numerous studies ascribed a sometimes bewildering variety of biological effects to both electromagnetic as well as static magnetic fields (1,2). It has been criticized that many investigations which deal with the biological impact of weak magnetic fields are hampered by shortcomings in experimental design and often also by a lack of reproducibility (2). As the vast majority of those reports is rather descriptive in nature, it is not surprising that the molecular or biophysical foundations for the alleged cell biological effects remain generally enigmatic (1,3). In the absence of a hypothetical mechanism to guide experimental design, proper adjustment and control of the experimental parameters are usually precluded. Only the knowledge of the spatiotemporal mechanisms of the magnetic field-induced effects will enable the deliberate exploitation of such signals, e.g. for the remote control of cellular signaling processes. Remote control of cellular functions is generally difficult, though worthwhile to attain, as it provides an opportunity for noninvasive, restricted manipulation of cell functions. Such technology can be exploited to tackle unsolved questions in spatial and temporal resolution of cell signaling and cross-talk, and may also contribute to the development of novel therapeutic strategies. For example in neurosciences, it is a common challenge to unravel electrical and chemical signals, which affect neurons as well as neuronal circuits, and to deduct how brain activity translates finally into complex behavior (4). One advanced technology to overcome such problems is to use genetically targeted photostimulation. This approach allows to study the connectivity and dynamics of neural circuits and to assign behavioral content to neurons and their activity pattern. At the same time, such information may provide a perspective for restoring neuronal information corrupted by injury or disease (4). Furthermore, optical switches have been developed for the remote and noninvasive control of cell signaling that can control receptors and ion channels (5). However, the utility of such methods is seriously limited by the accessibility of target cells to light and by the invasiveness required for light application. Appropriate magnetic fields, on the other hand, might either directly or indirectly serve as tools for the remote control of cell functions. In contrast to electric fields, magnetic fields are much less attenuated in tissues. Hence, they can intrude into deeper layers of tissue, where they could modulate biochemical processes leading to changes in signaling pathways and cell biological events (1). In this context, we explored the cellular and molecular effects of specifically designed high-performance micro- magnet arrays. Our preliminary data prompted us then to address their potential for remote control of cell function. In contrast to conventional high-performance magnets, which generate low-gradient magnetic fields, the micro-magnet arrays utilized here are characterized by high-gradient magnetic fields, which are not encountered in the environment and which therefore appear to be predestined for potential application in the remote modulation of cell function. Our study demonstrates that fibroblasts and monocytic cells respond specifically to high- gradient magnetic fields generated by high- performance micro-magnet arrays. The cellular response involves increased intracellular calcium levels ([Ca2+ ]i), which cannot be achieved with low-gradient magnetic fields produced by conventional high-performance bulk magnets. Not unexpected, when [Ca2+ ]i was continuously elevated for extended periods of time, apoptotic cell death occurred, whereas temporally restricted application of the high- gradient magnetic fields allowed remote control of cell function as exemplified by fibroblasts transdifferentiation. Moreover, our study identifies TRPV4 cation channels as cellular magnetoeffectors, which mediate Ca2+ influx in response to the high-gradient magnetic fields. Thus, we discovered a new mode of remotely controlling TRPV4 channel activation in the absence of other activators. This is the first report that demonstrates a clear effector mechanism for magnetic fields with high gradients, which are not encountered in the environment. EXPERIMENTAL PROCEDURES Manufacture of High Performance Micro-Magnet Arrays The micro-magnet THIS MANUSCRIPT HAS BEEN WITHDRAWN AT THE AUTHOR'