ADVANCING BRAIN REPAIR: SYNAPTIC MECHANO-GENETIC TOOLS FOR RESTORING NEURAL CONNECTIVITY

We are developing a mechano-genetic technology to regulate functional connectivity in neural circuits and to explore its therapeutic potential in high-prevalence treatment-resistant brain disorders. Mechano-genetics is an emerging neuromodulation strategy that combines cell-type specificity, achieved through genetically encoded actuators, with the ability of magnetic fields to penetrate biological tissue non-invasively. Despite promising proof-of-concept studies, the translation towards functional circuit studies has been limited by insufficient spatial resolution and control over force delivery.
Here, we introduce an advanced mechano-genetic platform that mechanically stimulates neurons using functionalized, biocompatible magnetic nanoparticles coupled to engineered mechanoreceptors expressed on neuronal membranes. Mechanical stimulation is delivered through magnetic tweezers, enabling precise control of force magnitude, direction and temporal dynamics. Using optimized magnetic field configurations, we can exert piconewton-scale forces at subcellular resolution.
We have developed a comprehensive toolkit including custom magnetic nanoparticles, mechanosensitive receptors and optical readouts to quantify neuronal and network-level responses to mechanical stimulation. By engaging endogenous mechanotransduction pathways, this approach is designed to enable bidirectional modulation of neuronal excitability and circuit activity.
Together, this interdisciplinary effort establishes a non-invasive and spatially precise framework for probing and repairing dysfunctional neural connectivity.