We propose neutron diffraction, x-ray diffraction, and NMR studies of the structural relationships between multilamellar liposomes, oriented lipid multilayers, and large paucilamellar vesicles. These bilayer systems are central to model and reconstitution studies of biomembrane function and to the development of new liposome technology for cell biology and drug delivery applications. Even though these systems have been widely studied in the past, the physiocochemical and structural relationships among them remain unclear. We are interested in these relationships and how they drive the formation of a particular system. The nature of the so-called repulsive hydration forces between the bilayers and how they are modified by orientation on surfaces are crucial to understanding these relationships. Our general goals are to: (1) determine the state of the lipid and water relative to the degree of hydration and orientation, (2) establish the conditions under which a given model system can be considered physiocochemically equivalent to another, and (3) investigate the structural basis for the hydration forces. The studies will be first performed on 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) to establish a reference standard. We will then examine how changes in head group density and volume affect the interbilayer forces. Surprisingly, the published studies of head group orientation and water distribution, while excellent, are quite incomplete. The most complete study available examined one lipid type at only two temperatures and hydrations. Our study will deal with lipids in the liquid crystalline state and will examine in detail head group orientation and water distribution versus hydration. Of particular importance are the studies we propose on large paucilamellar vesicles which have never been examined systematically by diffraction techniques.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM037291-03
Application #
3292587
Study Section
(SSS)
Project Start
1986-07-01
Project End
1990-06-30
Budget Start
1988-07-01
Budget End
1990-06-30
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Type
Schools of Medicine
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697