Abstract

Astrocytes play crucial and diverse roles in brain health and disease. The ability to selectively control astrocytes provides a valuable tool for understanding their function and has the therapeutic potential to correct dysfunction. Existing technologies such as optogenetics and chemogenetics require the introduction of foreign proteins, which adds a layer of complication and hinders their clinical translation. We have developed a novel technique, magnetomechanical stimulation (MMS), that enables remote and selective control of astrocytes without genetic modification. MMS exploits the mechanosensitivity of astrocytes and triggers mechano-gated calcium and adenosine triphosphate (ATP) signalling by applying a magnetic field to antibody-functionalised magnetic particles that are targeted to astrocytes. Using purpose-built magnetic devices, we determined the mechanosensory threshold of astrocytes, identified a sub-micrometre particle for effective MMS, established the in vivo fate of the particles, and induced cardiovascular responses in rats after delivering particles to specific brainstem astrocytes. By eliminating the need for device implantation and genetic modification, MMS is a method for controlling astroglial activity with an improved prospect for clinical application than existing technologies.