We report a strategy for using magnetic Janus microparticles to control the stimulation of T cell signaling with single-cell precision. To achieve this, we design Janus particles that are magnetically responsive on one hemisphere and stimulatory to T cells on the other side. By manipulating the rotation and locomotion of Janus particles under an external magnetic field, w e control the orientation of the particle-cell recognition and thereby initiation of T cell activation. This study demonstrates a step towards employing anisotropic material properties of Janus particles to control single cell activities without the need of complex magnetic manipulation devices.
KeywordsJanus particle; magnetic properties; nanotechnology; colloids; Immunology Cells sense their environment and signal one another via receptor-ligand recognition. The binding of ligands to specialized cell surface receptors activates intracellular signaling pathways that determine the behavior of cells. Our ability to regulate these signaling events is essential for not only fundamental understanding of cell biology, but also engineering of cell functions for treating diseases. [1] Among the various strategies for controlling cell signaling with external stimuli, magnetic manipulation is widely used owing to its unique advantages, such as the precise control over the intensity and direction of magnetic forces as well as minimal damage to living cells, in comparison to optical techniques. [1a, 2] Rotating magnetic field has been used to twist magnetic nanoparticles to control the opening of ion channels, [3] measure the mechanical properties of the cell cytoplasm and cytoskeleton, [4] and probe the mechanotransduction of cell surface receptors. [5] Local heating of magnetic nanoparticles has also been exploited to activate temperature-sensitive ion channels in neuron cells. [1a] A few groups used the aggregation of magnetic nanoparticles as a switch to activate cell signaling. [2a-c, 6] In those studies, magnetic nanoparticles were coated with ligands specific for a target signaling pathway, [2a, 2c, 6a, 6b] such as the apoptosis of tumor cells [6d] or immune cell stimulation. [2b, 6c] When nanoparticles aggregated under the influence of a magnetic field, they induced the clustering of the membrane receptors to * yy33@indiana.edu.Supporting information for this article is given via a link at the end of the document.
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Author ManuscriptAuthor Manuscript which they were bound, which triggered the desired cell responses. A similar strategy has also been used with nanoparticles inside cells to regulate the nucleation and assembly of cytoskeleton proteins. [7] However, these methods do not allow control of signaling with single-cell precision, because the aggregation of magnetic nanoparticles cannot be controlled locally, unless a complex apparatus such as magnetic tweezer is used to generate localized magnetic fields. [8] Here, we present a strategy that employs magnetic Janus microparti...