@article{Han2024,

title = {Janus microparticles-based targeted and spatially-controlled piezoelectric neural stimulation via low-intensity focused ultrasound},

author = {Mertcan Han and Erdost Yildiz and Ugur Bozuyuk and Asli Aydin and Yan Yu and Aarushi Bhargava and Selcan Karaz and Metin Sitti},

editor = {Nature Publishing Group UK London},

url = {https://www.nature.com/articles/s41467-024-46245-4#citeas},

doi = {https://doi.org/10.1038/s41467-024-46245-4},

year  = {2024},

date = {2024-03-05},

journal = {Nature Communications},

volume = {15},

issue = {1},

pages = {2013},

abstract = {Electrical stimulation is a fundamental tool in studying neural circuits, treating neurological diseases, and advancing regenerative medicine. Injectable, free-standing piezoelectric particle systems have emerged as non-genetic and wireless alternatives for electrode-based tethered stimulation systems. However, achieving cell-specific and high-frequency piezoelectric neural stimulation remains challenging due to high-intensity thresholds, non-specific diffusion, and internalization of particles. Here, we develop cell-sized 20 μm-diameter silica-based piezoelectric magnetic Janus microparticles (PEMPs), enabling clinically-relevant high-frequency neural stimulation of primary neurons under low-intensity focused ultrasound. Owing to its functionally anisotropic design, half of the PEMP acts as a piezoelectric electrode via conjugated barium titanate nanoparticles to induce electrical stimulation, while the nickel-gold nanofilm-coated magnetic half provides spatial and orientational control on neural stimulation via external uniform rotating magnetic fields. Furthermore, surface functionalization with targeting antibodies enables cell-specific binding/targeting and stimulation of dopaminergic neurons. Taking advantage of such functionalities, the PEMP design offers unique features towards wireless neural stimulation for minimally invasive treatment of neurological diseases.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Yildiz2024,

title = {Experimental model for strain-induced mechanical neurostimulation on human progenitor neurons},

author = {Erdost Yildiz and Mertcan Han and Linda Werneck and Marc-Andre Keip and Metin Sitti and Michael Ortiz},

editor = {Science Communications World Wide},

url = {https://www.world-wide.org/fens-24/experimental-model-strain-induced-mechanical-5cbdf455/},

doi = {https://doi.org/10.57736/a03c-08e1},

year  = {2024},

date = {2024-01-01},

journal = {Science Communications World Wide},

abstract = {Aim: Although non-invasive, such as focused ultrasound stimulation, and invasive, such as neural interface implantations, neurological interventions on the brain are increasing in the clinics nowadays, there is no detailed experimental model of these mechanical effects on neurons. In this study, we built an experimental model to mimic mechanical strain stress on neurons and compared the experimental model's effectiveness with the existing literature. Methods: In this study, we designed unidirectional, bidirectional, and omnidirectional strain setups integrated with a high-speed camera. Neural membrane potentials and intracellular calcium levels were calculated with a custom algorithm based on the calcium signal collected with Fluo-4 from RenCell human progenitor neurons, which was strained up to 20%. During this analysis, confounding effects of motion, strain, and background were removed with a custom-made algorithm. Results: In these experiments, human progenitor neurons subjected to instantaneous omnidirectional strain stress application above 15% generate action potential responses. While the action potential generation behavior is related to fast intracellular calcium influx, slow internal calcium increase due to strain application is not associated with action potential propagation. Conclusion: In this study, we have produced an experimental model for reproducible omnidirectional strain stress application and determined the threshold strain-stress values of action potential propagation behavior in human progenitor neurons. These results from this experimental model can be combined with theoretical models, such as the Hodgkin & Huxley model, and can be an effective simulation tool for future clinical applications.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Werneck2023,

title = {A Simple Quantitative Model of Neuromodulation. Part I: Ion Flow Through Neural Ion Channels},

author = {Linda Werneck and Mertcan Han and Erdost Yildiz and Marc-André Keip and Metin Sitti and Michael Ortiz},

editor = {Biological Physics},

url = {https://arxiv.org/abs/2309.01393},

doi = {https://doi.org/10.48550/arXiv.2309.01393},

year  = {2023},

date = {2023-09-04},

journal = {Biological Physics},

abstract = {We develop a simple model of ionic current through neuronal membranes as a function of membrane potential and extracellular ion concentration. The model combines a simplified Poisson-Nernst-Planck (PNP) model of ion transport through individual mechanosensitive ion channels with channel activation functions calibrated from ad hoc in-house experimental data. The simplified PNP model is validated against bacterial Gramicidin A ion channel data. The calibrated model accounts for the transport of calcium, sodium, potassium, and chloride and exhibits remarkable agreement with the experimentally measured current-voltage curves for the differentiated human neural cells. All relevant data and code related to the ion flow models are available at DaRUS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}