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Courtesy Photo | Microelectrode array (MEA) with cell guide. The NMJ model is established on a MEA…… read more read more
Courtesy Photo | Microelectrode array (MEA) with cell guide. The NMJ model is established on a MEA surface to enable spatially localized detection of neuromuscular signals resulting from the firing of the synapse. The cell guide mounted on the array is part of the process of growing the muscle and nerve cells with the right anatomical organization. (DTRA image) Multiwell system with LED: The NMJ is established in culture dishes like this to start development of a high throughput NMJ model system. For this prototype, a custom-made array of LED lights allows multiple NMJ setups to simultaneously be stimulated with light to trigger nerve firing. (DTRA image) see less | View Image Page
The nervous system is the body’s network for receiving input from the senses, for telling muscles how to move, and for managing involuntary functions like breathing and maintaining normal blood flow. Because the nervous system does so many things, any new tool is desirable that helps researchers better understand its function which then helps to develop treatments to prevent or fix problems. In research supported by the Defense Threat Reduction Agency’s (DTRA) Chemical and Biological Technologies Department in its role as the Joint Science and Technology Office (JSTO), Los Alamos National Laboratory (LANL) is developing a two-dimensional cellular model that recreates the function of a nerve cell forming a connection, called a synapse, with a muscle.
A synapse is a structure formed when a signaling nerve cell makes contact with another cell receiving the signal. The kinds of cells that can receive nerve signals include other nerve cells as well as muscle cells. When the nerve signal is being sent to a muscle, the structure formed in a synapse is called a neuromuscular junction (NMJ). Muscle cells must receive nerve signals to tell them to contract or extend to initiate movement, such as voluntarily bending an arm or involuntarily moving food through the digestive system after eating. Many diseases are caused by problems at the NMJ, such as those resulting from nerve agents and pesticides, botulinum and tetanus toxins, and snake venom.
The LANL model allows a nerve signal to be triggered on demand to measure the response of muscle cells to the nerve signal. To develop the model, LANL solved several challenges, including how to grow their nerve cells and muscle cells together in a dish. The team formulated a cell growth medium that caused both cell types to simultaneously mature properly. To trigger the muscle cells on demand, they programmed the nerve cells to generate a signal after exposure to light.
To make signal detection easier, researchers programmed the muscle cells to amplify the signal from the nerve cells. They then grew the whole NMJ on an electrode that allowed sensitive detection of muscle cell activation by nerve signals through the NMJ. The combination of nerve and muscle cells grown together supports proper forming of the NMJ. Being able to activate the NMJ with light to detect the resulting activity on an electrode creates a useful model of the NMJ.
Using this model will allow easier study of those problems and enable testing for drugs that may prevent or treat the associated adverse effects. For example, when discovering a new chemical weapon, this NMJ model will allow for rapid and inexpensive testing to determine the weapon’s effects and to assess drug molecules.
As protective and therapeutic treatments are developed, this model will be a powerful tool for testing and improving the treatments and decreasing the reliance on expensive, time-consuming animal experimentation. Also, as the methods for creating the NMJ model on electrodes improve, it may be possible to have portable NMJ models that can be used as sensitive bioelectric chemical or biological agent detectors to better protect warfighters.
POC: Michael Stockelman, [email protected]
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