The objective of this research is to obtain quantitatively accurate characterizations of the molecular organization of lipid molecules in bilayers. Such characterization is essential to test the hypothesis that the differences in lipid composition in different biomembranes in the body are related to structural differences in the underlying lipid bilayers that would be required for healthy cell function. The primary proposed technique is x-ray scattering which will be complemented by our volumetric measurements, as well as results from other laboratories using NMR, IR and molecular dynamics simulations. Electron density profiles of bilayers, composed primarily of phosphatidylcholine and phosphatidylethanolamine lipids with varying chain length and unsaturation, will be obtained at higher spatial resolution in the biologically relevant L-alpha phase. Bilayer preparations will include (i) multilamellar vesicles, (ii) oriented samples on solid substrates and (ill) unilamellar vesicles. Together with our determinations of gel phase structure, the area per lipid AF and the thickness of these bilayers will be determined. Thermal expansivity and the effects of temperature on membrane fluidity will be determined by measuring over wider temperature ranges. A necessary intermediate step will be to establish the dehydration threshold for structural invariance, so that less than fully hydrated and oriented samples with more orders of reflection can be studied, with the assurance that they have the same structure as fully hydrated bilayers. It is proposed to continue using the CHESS facility to obtain data at the necessary high instrumental resolution that can only be achieved for lipid bilayer samples with the high x-ray flux of synchrotron sources. These synchrotron studies will also yield information about the undulation fluctuations that play a role in interbilayer interactions. In addition, intrabilayer fluctuations that are necessary for functioning biomembranes will be studied by measuring wide angle diffuse scattering.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM044976-10
Application #
6018813
Study Section
Biophysical Chemistry Study Section (BBCB)
Project Start
1990-07-01
Project End
2001-11-30
Budget Start
1999-07-01
Budget End
2001-11-30
Support Year
10
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Carnegie-Mellon University
Department
Physics
Type
Schools of Arts and Sciences
DUNS #
052184116
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Nagle, John F; Jablin, Michael S; Tristram-Nagle, Stephanie (2016) Sugar does not affect the bending and tilt moduli of simple lipid bilayers. Chem Phys Lipids 196:76-80
Stetten, Amy Z; Moraca, Grace; Corcoran, Timothy E et al. (2016) Enabling Marangoni flow at air-liquid interfaces through deposition of aerosolized lipid dispersions. J Colloid Interface Sci 484:270-278
Nagle, John F; Akabori, Kiyotaka; Treece, Bradley W et al. (2016) Determination of mosaicity in oriented stacks of lipid bilayers. Soft Matter 12:1884-91
O'Neil, Lauren; Andenoro, Kathryn; Pagano, Isabella et al. (2016) HIV-1 matrix-31 membrane binding peptide interacts differently with membranes containing PS vs. PI(4,5)P2. Biochim Biophys Acta 1858:3071-3081
Reese, Caleb W; Strango, Zachariah I; Dell, Zachary R et al. (2015) Structural insights into the cubic-hexagonal phase transition kinetics of monoolein modulated by sucrose solutions. Phys Chem Chem Phys 17:9194-204
Neale, Chris; Huang, Kun; GarcĂ­a, Angel E et al. (2015) Penetration of HIV-1 Tat47-57 into PC/PE Bilayers Assessed by MD Simulation and X-ray Scattering. Membranes (Basel) 5:473-94
Nagle, John F; Jablin, Michael S; Tristram-Nagle, Stephanie et al. (2015) What are the true values of the bending modulus of simple lipid bilayers? Chem Phys Lipids 185:3-10
Kollmitzer, Benjamin; Heftberger, Peter; Podgornik, Rudolf et al. (2015) Bending Rigidities and Interdomain Forces in Membranes with Coexisting Lipid Domains. Biophys J 108:2833-42
Akabori, Kiyotaka; Nagle, John F (2015) Structure of the DMPC lipid bilayer ripple phase. Soft Matter 11:918-26
Ma, Yicong; Ghosh, Sajal K; Bera, Sambhunath et al. (2015) Accurate calibration and control of relative humidity close to 100% by X-raying a DOPC multilayer. Phys Chem Chem Phys 17:3570-6

Showing the most recent 10 out of 48 publications