Syracuse University Magazine

Research Snapshot


Project: Enabling transport across the blood-brain barrier by engineering thermodynamically favorable pathways

Investigator: Shikha Nangia

Department: Biomedical and Chemical Engineering

Sponsor: National Science Foundation/Faculty Early Career Development (CAREER) Award

Amount Awarded: $500,000 (April 1, 2015-March 31, 2020)

Background:  The blood-brain barrier plays a critical role of allowing only certain types of molecules to enter the brain from the blood stream. This important capability protects the brain from exposure to harmful chemical compounds. However, it also prevents certain drugs from entering the brain to treat brain disorders or diseases, such as Alzheimer’s disease. Since the segment of the U.S. population older than 65 is expected to increase by 50 percent by 2030, and the cost of care to treat patients with these kinds of brain diseases is billions of dollars per year, finding new ways to help drugs cross the blood-brain barrier would provide significant benefits to patients and the nation. Nevertheless, understanding how therapeutic drug molecules move or don’t move across the barrier into the brain has remained elusive. The proposed research will combine existing theories in a new way to understand how this movement is controlled across the blood-brain barrier, and will use an extensive computational toolkit to engineer favorable pathways to transcend it.

Impact:  The proposed project will provide new molecular-level strategies to deliver drug molecules to the brain, and characterize the thermodynamics and transport kinetics of the blood-brain barrier. The focus will be to elucidate the molecular structure of the tight junctions responsible for preventing the passage of molecules and ions through the space between adjacent cells. These goals will be achieved using a combination of molecular docking, analytical tools, and multiscale molecular dynamics. Additionally, the thermodynamics of the transport process properties of ions, water, and small drug molecules will be computed. The computed transport rates will be combined with stochastic simulation algorithm simulations to compute effective transport properties of drugs across the tight junction strands. The project also features an education plan that integrates findings from the research objectives with active-learning pedagogies to more effectively teach undergraduate and graduate thermodynamics courses.


The snapshots illustrate the  self-assembly process of Claudin-5 proteins (red) in the lipid membrane (green, blue, yellow) at 0, 1.5, 4.5, and 10 microseconds leading to the blood-brain barrier tight junctions.