Our research focuses on the molecular organization, dynamics, and interactions of the chemical constituents in biological membranes. The goal of our research is the identification of the molecular mechanisms through which membrane associated phenomena (e.g. ligand-receptor coupling, conduction of electrical impulses, and ion transport) are mediated.

Recently we have identified plasmalogens as the major phospholipid constituents of sarcolemma, a specialized membrane in heart cells which is responsible for electrical conduction. Plasmalogens differ from conventional diacyl phospholipids (e.g. phosphatidylcholine) by the presence of a vinyl ether linkage in the proximal portion of the sn-l aliphatic chain. To understand the biologic significance of plasmalogens in the membrane bilayer, we initially explored two hypotheses: 1) plasmalogens have substantially different molecular dynamics than their diacyl phospholipid counterparts facilitating the function of specific transmembrane proteins; and 2) phospholipases are present in biological tissues which selectively hydrolyze plasmalogen substrates facilitating signal transduction across biological membranes. To explore these hypotheses we have synthesized radiolabeled, deuterated, photoaffinity labeled and spin labeled plasmalogens to identify the biological reasons underlying the predominance of plasmalogens in sarcolemmal membranes. In regard to the first hypothesis, we have demonstrated that substantial alterations in membrane molecular dynamics are present in phospholipid bilayers comprised of plasmalogen molecular species in comparison to diacyl phospholipids. In regard to the second hypothesis, many biologic phenomena are mediated by the specific release of arachidonic acid after ligand-receptor coupling. Since the overwhelming majority of arachidonic acid in several tissues is present in plasmalogen molecular species, we have focused on identifying, purifying, and characterizing the phospholipases which selectively hydrolyze plasmalogen substrates. Recently we have identified two phospholipases which selectively cleave plasmalogen substrates.

To further explore these hypotheses, our current projects include:

1. The role of membrane organization and physical properties in modulating protein-protein interactions, ion channel function and membrane fusion.

2. The synthesis of novel photoaffinity reagents to identify the active site of intracellular phospholipases and other signal-transducing proteins.

3. The self-assembly of drugs in plasmalogen membranes and targeted drug delivery to plasmalogen membranes.

4. The chemical mechanisms which result in the activation of intracellular phospholipases.
   
   

Our research utilizes a wide variety of physical (NMR, UV-VIS and fluorescence spectroscopy), separative (HPLC, FPLC), and analytical techniques (electrosprayUtilizing these techniques we hope to obtain a better ionization MS, fast atom bombardments MS, capillary electrophoresis and GC-MS). understanding of thepresent in cell membranes which follow each cell to fulfill its biologic chemical mechanisms underlying the specific molecular interactions function.

FIGURE 1: Comparison of deuterium magnetic resonance spectra of specifically deuterated phosphatidylcholine and plasmenylcholine.