Magnetically triggered release of active TGF-B from spin vortex microdiscs

Abstract Transforming Growth Factor-β (TGF-β) has been implicated in a variety of cellular functions, including control of cell cycle, cell proliferation, extracellular matrix formation, and even stem cell differentiation. TGF-β is also a contributor for combinatorial cellular responses, including cellular senescence, cellular apoptosis, and tumor progression. As a result, spatial and temporal control of TGF-β delivery has the potential to lead to greater control over cell signaling while minimizing the potential for undesirable off-target effects. We recently reported magnetically triggered release of active TGF-β from TGF-β Latent Complex conjugated to high-specific absorption rate (SAR) magnetic nanoparticles via magnetic hyperthermia; here we redirected our approach to spin vortex discs. Planar, gold-coated Permalloy (Ni80Fe20) microdiscs (∼2.0 µm diameter, 70 nm thick) were fabricated via standard lithography techniques and thin-film deposition. The discs were then bioconjugated with latent TGF-β via gold-thiol conjugation chemistry, and shear stress on the attached latent TGF-β was induced via magnetic actuation of the discs. This magnetic actuation was achieved via application of a spatially uniform dual pulsating magnetic field (∼1 mT) using two perpendicular pairs of Helmholtz coils at a frequency of 20 Hz for 1 hour. Preliminary results of the bioconjugated discs shown here indicate a significant increase in the release of active TGF-β compared to the baseline passive release. Further studies will focus on investigating non-invasive remote activation and direction of TGF-β by a magnetic field, as well as investigating the potential of expanding this work to other growth factors that exist in latent and active forms.