The first broad objective of this research is to obtain quantitatively accurate structure of fully hydrated lipid bilayers with and without added components such as peptides. 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 are required for membrane protein functionality and healthy cell function. The results of the proposed work will guide and evaluate molecular dynamics simulations. The second broad objective is to obtain quantitatively accurate interactions between bilayers, which are useful for understanding membrane adhesion and fusion. Study of these interactions involves nanoscale properties of membranes, such as the bending modulus, area compressibility and thermal expansion coefficient, which are input data for considering membrane morphology and cell shape changes. Our primary technique is x-ray diffraction which will be complemented by our volumetric measurements, as well as with data from other laboratories, such as NMR, neutron diffraction and molecular dynamics simulations. We have made a new breakthrough that enables study of oriented membrane preparations in the fully hydrated, biologically relevant fluid phase. Oriented samples have the advantage that the data extend to higher q, so more complete structures can be obtained. We have developed an analysis that extracts both structural and fluctuational information from these data to address both of our broad objectives. This novel method will be appropriate for studying a variety of biomembrane systems. We propose to apply it to the HIV fusion peptide to determine the depth of penetration of the N-terminus into the hydrophobic region of lipid bilayers.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM044976-12
Application #
6621274
Study Section
Biophysical Chemistry Study Section (BBCB)
Program Officer
Chin, Jean
Project Start
1990-07-01
Project End
2005-11-30
Budget Start
2002-12-01
Budget End
2003-11-30
Support Year
12
Fiscal Year
2003
Total Cost
$248,998
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

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