Magnetic
nanomaterials in magnetic fields can serve as versatile
transducers for remote interrogation of cell functions. In this study,
we leveraged the transition from vortex to in-plane magnetization
in iron oxide nanodiscs to modulate the activity of mechanosensory
cells. When a vortex configuration of spins is present in magnetic
nanomaterials, it enables rapid control over their magnetization direction
and magnitude. The vortex configuration manifests in near zero net
magnetic moment in the absence of a magnetic field, affording greater
colloidal stability of magnetic nanomaterials in suspensions. Together,
these properties invite the application of magnetic vortex particles
as transducers of externally applied minimally invasive magnetic stimuli
in biological systems. Using magnetic modeling and electron holography,
we predict and experimentally demonstrate magnetic vortex states in
an array of colloidally synthesized magnetite nanodiscs 98–226
nm in diameter. The magnetic nanodiscs applied as transducers of torque
for remote control of mechanosensory neurons demonstrated the ability
to trigger Ca2+ influx in weak (≤28 mT), slowly
varying (≤5 Hz) magnetic fields. The extent of cellular response
was determined by the magnetic nanodisc volume and magnetic field
conditions. Magnetomechanical activation of a mechanosensitive cation
channel TRPV4 (transient receptor potential vanilloid family member
4) exogenously expressed in the nonmechanosensitive HEK293 cells corroborated
that the stimulation is mediated by mechanosensitive ion channels.
With their large magnetic torques and colloidal stability, magnetic
vortex particles may facilitate basic studies of mechanoreception
and its applications to control electroactive cells with remote magnetic
stimuli.
Connecting neural circuit output to behaviour can be facilitated by precise chemical manipulation of specific cell populations 1,2. Engineered receptors exclusively activated by designer small molecules enable manipulation of specific neural pathways 3,4. Their application to studies of behaviour has thus far been hampered by a trade-off between low temporal resolution of systemic injection versus invasiveness of implanted cannulas or infusion pumps 2. Here, we develop remotely controlled chemomagnetic modulation-a nanomaterials-based technique that permits pharmacological interrogation of targeted neural populations in freely moving subjects. The heat Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:
Understanding the function of nitric oxide (NO), a lipophilic messenger in physiological processes across nervous, cardiovascular and immune systems, is currently impeded by the dearth of tools to deliver this gaseous molecule
in situ
to specific cells. To address this need, we developed iron sulfide nanoclusters that catalyse NO generation from benign sodium nitrite in the presence of modest electric fields. Locally generated NO activates the NO-sensitive cation channel, transient receptor potential vanilloid family member 1 (TRPV1), and latency of TRPV1-mediated Ca
2+
responses can be controlled by varying the applied voltage. Integrating these electrocatalytic nanoclusters with multimaterial fibres allows NO-mediated neuronal interrogation
in vivo
.
In situ
generation of NO within the ventral tegmental area via the electrocatalytic fibres evoked neuronal excitation in the targeted brain region and its excitatory projections. This NO generation platform may advance mechanistic studies of the role of NO in the nervous system and other organs.
The field of bioelectronic medicines seeks to modulate electrical signaling within peripheral organs, providing temporally precise control of physiological functions. This is usually accomplished with implantable devices, which are often unsuitable for interfacing with soft and highly vascularized organs. Here, we demonstrate an alternative strategy for modulating peripheral organ function, which relies on the endogenous expression of a heat-sensitive cation channel, transient receptor potential vanilloid family member 1 (TRPV1), and heat dissipation by magnetic nanoparticles (MNPs) in remotely applied alternating magnetic fields. We use this approach to wirelessly control adrenal hormone secretion in genetically intact rats. TRPV1-dependent calcium influx into the cells of adrenal cortex and medulla is sufficient to drive rapid release of corticosterone and (nor)epinephrine. As altered levels of these hormones have been correlated with mental conditions such as posttraumatic stress disorder and major depression, our approach may facilitate the investigation of physiological and psychological impacts of stress.
Genetic variants in the human ortholog of acid-sensing ion channel-1a subunit (ASIC1a) gene are associated with panic disorder and amygdala dysfunction. Both fear learning and activity-induced long-term potentiation (LTP) of cortico-basolateral amygdala (BLA) synapses are impaired in ASIC1a-null mice, suggesting a critical role of ASICs in fear memory formation. In this study, we found that ASICs were differentially expressed within the amygdala neuronal population, and the extent of LTP at various glutamatergic synapses correlated with the level of ASIC expression in postsynaptic neurons. Importantly, selective deletion of ASIC1a in GABAergic cells, including amygdala output neurons, eliminated LTP in these cells and reduced fear learning to the same extent as that found when ASIC1a was selectively abolished in BLA glutamatergic neurons. Thus, fear learning requires ASIC-dependent LTP at multiple amygdala synapses, including both cortico-BLA input synapses and intra-amygdala synapses on output neurons.
The eHealth trend has spread globally. Internet of Things (IoT) devices for medical service and pervasive Personal Health Information (PHI) systems play important roles in the eHealth environment. A cloud-based PHI system appears promising but raises privacy and information security concerns. We propose a cloud-based fine-grained health information access control framework for lightweight IoT devices with data dynamics auditing and attribute revocation functions. Only symmetric cryptography is required for IoT devices, such as wireless body sensors. A variant of ciphertext-policy attribute-based encryption, dual encryption, and Merkle hash trees are used to support fine-grained access control, efficient dynamic data auditing, batch auditing, and attribute revocation. Moreover, the proposed scheme also defines and handles the cloud reciprocity problem wherein cloud service providers can help each other avoid fines resulting from data loss. Security analysis and performance comparisons show that the proposed scheme is an excellent candidate for a cloud-based PHI system.
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