Year: 2024
Type: article
Abstract: Technologies for neuromodulation have rapidly developed in the past decade with a particular emphasis on creating noninvasive tools with high spatial and temporal precision. The existence of such tools is critical in the advancement of our understanding of neural circuitry and its influence on behavior and neurological disease. Existing technologies have employed various modalities, such as light, electrical, and magnetic fields, to interface with neural activity. While each method offers unique advantages, many struggle with modulating activity with high spatiotemporal precision without the need for invasive tools. One modality of interest for neuromodulation has been the use of mechanical force. Mechanical force encapsulates a broad range of techniques, ranging from mechanical waves delivered via focused ultrasound (FUS) to torque applied to the cell membrane.Mechanical force can be delivered to the tissue in two forms. The first form is the delivery of a mechanical force through focused ultrasound. Energy delivery facilitated by FUS has been the foundation for many neuromodulation techniques, owing to its precision and penetration depth. FUS possesses the potential to penetrate deeply (∼centimeters) into tissue while maintaining relatively precise spatial resolution, although there exists a trade-off between the penetration depth and spatial resolution. FUS may work synergistically with ultrasound-responsive nanotransducers or devices to produce a secondary energy, such as light, heat, or an electric field, in the target region. This layered technology, first enabled by noninvasive FUS, overcomes the need for bulky invasive implants and also often improves the spatiotemporal precision of light, heat, electrical fields, or other techniques alone. Conversely, the second form of mechanical force modulation is the generation of mechanical force from other modalities, such as light or magnetic fields, for neuromodulation via mechanosensitive proteins. This approach localizes the mechanical force at the cellular level, enhancing the precision of the original energy delivery. Direct interaction of mechanical force with tissue presents translational potential in its ability to interface with endogenous mechanosensitive proteins without the need for transgenes.In this Account, we categorize force-mediated neuromodulation into two categories: 1) methods where mechanical force is the primary stimulus and 2) methods where mechanical force is generated as a secondary stimulus in response to other modalities. We summarize the general design principles and current progress of each respective approach. We identify the key advantages of the limitations of each technology, particularly noting features in spatiotemporal precision, the need for transgene delivery, and the potential outlook. Finally, we highlight recent technologies that leverage mechanical force for enhanced spatiotemporal precision and advanced applications.
Source: Accounts of Chemical Research
Institution: Stanford University
Language: English
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Open Access status: green
Funders: National Science Foundation, Spinal Muscular Atrophy Foundation, Rita Allen Foundation, Stanford University, Focused Ultrasound Foundation, Harvard University, Peking University, National Institutes of Health, University of California, San Diego, Wu Tsai Neurosciences Institute, Stanford University, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, Division of Chemical, Bioengineering, Environmental, and Transport Systems
Awards: NRT: NeuroTech - Bringing Technology to Neuroscience, G2911450482, CAREER: Sculpting light in biological tissue: an ultrasound-mediated traveling light source for spatiotemporally precise in vivo gene editing, Rapid brain-wide optogenetic screening with a noninvasive, dynamically programmable in vivo light source, Graduate Research Fellowship Program (GRFP), G6671297155, G6865427349, G733869539, Graduate Training Program in Biotechnology
OpenAlex ID: W4395069281