Cottrell College Science Awards - 2015
Effects of Cholesterol and Lipid Sorting on Aggregation of Nicotinic Acetylcholine Receptors
Cholesterol isn’t just some pesky substance to be avoided in food because it clogs the arteries. It’s a vital component of every cell membrane in our bodies, and it interacts in subtle but important ways with many other molecules responsible for life.
Unfortunately, we don’t understand all of those interactions.
Grace Brannigan, assistant professor of physics at Rutgers University-Camden, has received a Cottrell College Science Award from Research Corporation for Science Advancement to study the highly specific impact of cholesterol on of nicotinic Acetylcholine Receptors (nAChR) in lipid membranes. These are brain cell receptor proteins that, once they receive the proper chemical signal, send an electrical signal in the brain cell.
(A lipid is a molecule in which one end is “water-loving” and the other end is “oil-loving.” This allows them to form a membrane that protects the inside of the cell from the outside and also contains proteins (like the nAChR) that receive messages from other cells. Cholesterol is one of the lipids that makes this membrane.)
NaChRs are highly sensitive to the concentration of cholesterol in their surrounding membranes, a fact that may eventually prove important in the investigation of neurological disorders such as schizophrenia, Alzheimer’s disease, Parkinson’s disease, and alcohol and nicotine addiction.
“Improved understanding of the interactions between nAChRs and cholesterol may help elucidate the role of cholesterol pathologies in the progression of these disorders,” Brannigan says, “as well as illuminate why significant reversible cognitive impairment is observed in some people receiving cholesterol-lowering drugs.”
Brannigan and her students will investigate two possible mechanisms through which cholesterol may modulate the receptor: possibly through cholesterol enrichment around the protein over short length scales, or by causing receptors to cluster. To make this determination they will use advanced computer software to simulate the Newtonian equations of motion for systems with hundreds to millions of particles, as well as additional software that specifically simulates the molecular dynamics of lipids.