Cholesterol-Phospholipid Interactions in Membranes

University Of North Carolina At Wilmington, Wilmington NC

Investigators

Abstract

With this award, the Chemical Structure, Dynamics and Mechanisms program is supporting fundamental research of Professor Paulo Almeida at the University of North Carolina Wilmington (UNCW) to address the organization of biological membranes from the point of view of the physical chemistry of interactions in the lipid bilayer. Professor Almeida will employ a combination of computer simulations, calorimetry, and fluorescence spectroscopy to investigate the nature and the strength of those interactions. Professor Almeida will further integrate the research and educational components of this project within a new program designed to improve the quantitative skills of undergraduate students in the STEM fields, especially chemistry, while fostering the connections between biological and physical sciences, as a means of bridging the communication gap between these disciplines. UNCW is a primarily undergraduate institution, where participation of undergraduate students in research is a high priority. What is distinctive in this project for undergraduate education is that it combines a fundamental problem of active research in biophysical chemistry with extensive use of quantitative methods. Undergraduates will be involved early on in their studies, emphasizing learning by doing. Lipid bilayers composed of sphingomyelin, unsaturated phospholipids, and cholesterol are the simplest model for the lipid component of the outer leaflet of eukaryotic plasma membranes. The interactions of cholesterol with the other lipids are of particular importance,and they remain poorly understood. Membranes of saturated phospholipids and cholesterol have been described as mixtures of liquid ordered and liquid disordered phases. However, no phase separation has been observed in binary mixtures. Alternatively, ordered phospholipids and cholesterol have been proposed to form a "condensed complex." The liquid ordered phase would then consist of these complexes. This research seeks to explore an alternative in which the liquid ordered phase is a thermodynamic state of the phospholipid, which is well populated in the presence of cholesterol but rare in its absence. The project is designed to test these competing hypotheses through computer simulations and experimental studies, and to determine the magnitudes of the interactions in lipid mixtures that increasingly mimic the composition of biological membranes.