Nearest Neighbor Recognition project
Cell membranes consist of a complex mixture of proteins, polar lipids and a variety of other lipophilic molecules. Because of their fluid state, it has proven to be exceedingly difficult to define the interactions between nearest-neighbors, and also the role that such interactions play in determining the two-dimensional structure and function of cell membranes. Over the past few years, we have developed a "nearest-neighbor recognition" (NNR) method as a promising new chemical approach for investigating the lateral organization of fluid phospholipid membranes. In essence, NNR measurements take molecular-level snapshots of membrane organization by detecting and quantifying the tendency of lipids to become nearest-neighbors. To date, virtually all of our NNR work has focused on lipid-lipid interactions.
Currently, we are seeking to apply the NNR method to the study of lipid-peptide interactions, lipid-protein interactions, and lipid-lipid interactions in the presence of natural and unnatural membrane-perturbing agents. More specifically, lipid-peptide experiments are part of a long-term effort that is being aimed at clarifying the "rules" governing the sorting of peripheral and integral proteins by lipids in fluid bilayers. Lipid-protein studies, in combination with transbilayer phospholipid interactions, will provide insight into a much-debated issue that has a direct bearing on the structure and function of cell membranes--an issue for which there is virtually no experimental data; that is, the “communication” between the inner and outer leaflets of lipid bilayers. Finally, the effects of selected general anesthetics and amyloid beta-peptides on lipid-lipid interactions are expected to provide fundamental insight into two problems that have major biomedical importance; that is, the mechanism by which general anesthetics function, and the molecular basis of Alzheimer's Disease.>
In this project, extensive use is made of organic synthesis, liposome formation and characterization and HPLC analysis.