Poster abstracts
Poster number 30 submitted by Brandon Neel
Modeling Ultrasound Stimuli in Simulations of Ion Channels for Sonogenetics
Brandon Neel (Department of Chemistry & Biochemistry, OSBP), Elakkiya Tamilselvan (Biophysics), Harsha Mandayam Bharathi (Department of Chemistry & Biochemistry), Marcos Sotomayor (Department of Chemistry & Biochemistry)
Abstract:
Optical activation of neurons using light-sensitive ion channels (optogenetics) has provided invaluable and unprecedented insight into neuronal circuits and brain function. However, optogenetics is limited by the depth that light can reach through brain tissue. An alternative methodology, termed sonogenetics, uses low-intensity ultrasound that can propagate through brain tissue to activate worm TRPN or human TRPA1 ion channel proteins transfected into selected neurons. Intriguingly, both proteins have a large number of ankyrin repeats that assemble in long solenoid like structures that might provide an elastic attachment to the cytoskeleton. While the molecular mechanisms by which ultrasound activates these ion channels are unknown, cholesterol and ankyrin repeats have been shown to be required for ultrasound-mediated activity of TRPA1. Here we present modeling efforts to simulate TRPN and TRPA1 structures in a hydrated membrane bilayer in the presence and absence of ultrasound stimuli. We have created all-atom models of TRPN and TRPA1 and equilibrated these systems, with and without cholesterol. In addition, we have developed an approach that allows us to incorporate ultrasound in the simulations as a global oscillatory change in system pressure. Simulations of TRPA1 using this approach, with and without constraints on ankyrin repeats to mimic cytoskeletal attachment, are ongoing. We expect that these simulations will provide insight into ultrasound effects on ion channels and may assist in engineering protein sensors for sonogenetics.
Keywords: Channel protein, Simulations, Sonogenetics