CONTACT INFORMATION
Professor: Mary L. Kraft
University of Illinois
600 S Mathews Ave
208 RAL, MC-712
Urbana, IL 61801
phone: 217-333-2228
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research

Plasma Membrane Organization and Function

Schematic of cell membraneThe cell plasma membrane, the selectively permeable barrier that surrounds every cell, plays a critical role in both healthy biological processes and disease.  The cell plasma membrane mediates the interactions between a cell and its surroundings, including cell adhesion, cell-cell recognition, nutrient uptake, and signal transduction. To coordinate these functions, the plasma membranes of mammalian cells are organized into distinct domains of differing protein and lipid composition. Although the plasma membrane is composed of hundreds of different lipid and protein species, many scientists believe that interactions between just a few components, namely cholesterol and sphingolipids, are very important for this organization.

Though the plasma membrane contains many different types of lipids, changes in the abundances of just two components, sphingolipids and cholesterol, are suspected to have a drastic effect on cellular function. The mechanisms for this lipid-mediated cell (dys)function are poorly understood. This is partially due to a lack of methods to image cholesterol andNanoSIMS of cell shows sphingolipid distribution sphingolipids in membranes without using fluorophores that may alter the lipid’s distribution and function. We have overcome this obstacle by using high-resolution secondary ion mass specctrometry (SIMS), performed with a Cameca NanoSIMS 50, to image metabolically incorporated, stable isotope-labeled cholesterol and sphingolipids in the plasma membrane with better than 100 nm lateral resolution. Our published work in Proceedings of the National Academy of Sciences USA and the Journal of Biological Chemistry established that the plasma membranes of fibroblast cells contain sphingolipid domains that are not enriched with cholesterol, but are dependent on the cytoskeleton. This work provides a completely new understanding of plasma membrane organization.

We are now combining this technique with traditional biochemical methods and complementary imaging modalities to currently intractable biomedical problems that involve lipid-mediated biological function. One of our current interests is in the roles of cholesterol and sphingolipids in influenza virus infection.

This project includes collaborations with Dr. Joshua Zimmerberg at the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health, and Dr. Peter Weber at the Glenn T. Seaborg Institute at Lawrence Livermore National Laboratory.