This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. To assess the validity of the raft hypothesis for the cellular plasma membrane we examined both the dynamics and equilibria of liquid-ordered (Lo) and liquid-disordered (Ld) phases in the brain-sphingomyelin (SPM) /dioleoylphosphatidylcholine (DOPC)/cholesterol model membrane system. Using the known phase diagram for this lipid system containing the phase boundary between the one-phase regions and the two-phase coexistence region of the Lo and Ld phases and an ESR spectral fitting method (New Method for Determining Tie-lines in Coexisting Membrane Phases using Spin-label ESR, Y.-W. Chiang, J. Zhao, J. Wu, Y. Shimoyama, G.W. Feigenson, J.H. Freed, Biophysica-Biochimica Acta 1668, 99-105,2005) from the linear superposition of boundary spectra, we determined one tieline thru the Lo+Ld coexistence region. Many pairs of Lo and Ld phase compositions can coexist at equilibrium for this ternary lipid system, so tielines are necessary to model rafts because they tell us which phase compositions coexist and therefore which pair of compositions best model the plasma membrane. If the Lo and Ld phases observed in the SPM/DOPC/cholesterol model system are physically similar to raft domains, then the dynamic parameters of spin probes in the model membranes determined from ESR spectral fitting should be similar to those of the same probe in plasma membranes. This was found to be true in that dynamic parameters from chain-labeled spin probes at the boundary compositions of the one tieline so far determined compared very well with dynamic parameters from the same spin probes in live cells (Coexisting Domains in the Plasma Membranes of Live Cells Characterized by ESR Spectroscopy, M.J. Swamy, L. Ciani, M. Ge, A.K. Smith, D. Holowka, B. Baird, and J.H. Freed, Biophys. J. 90, 4452-4465, 2006). A more extensive analysis of Lo and Ld phase equilibria and dynamic comparison between model and real plasma membranes will require the determination of the entire set of tielines for the Lo+Ld phase coexistence region.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
2P41RR016292-11
Application #
8363975
Study Section
Special Emphasis Panel (ZRG1-BCMB-K (40))
Project Start
2011-09-01
Project End
2012-08-31
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
11
Fiscal Year
2011
Total Cost
$3,659
Indirect Cost
Name
Cornell University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Jain, Rinku; Vanamee, Eva S; Dzikovski, Boris G et al. (2014) An iron-sulfur cluster in the polymerase domain of yeast DNA polymerase ?. J Mol Biol 426:301-8
Pratt, Ashley J; Shin, David S; Merz, Gregory E et al. (2014) Aggregation propensities of superoxide dismutase G93 hotspot mutants mirror ALS clinical phenotypes. Proc Natl Acad Sci U S A 111:E4568-76
Georgieva, Elka R; Borbat, Peter P; Ginter, Christopher et al. (2013) Conformational ensemble of the sodium-coupled aspartate transporter. Nat Struct Mol Biol 20:215-21
Airola, Michael V; Sukomon, Nattakan; Samanta, Dipanjan et al. (2013) HAMP domain conformers that propagate opposite signals in bacterial chemoreceptors. PLoS Biol 11:e1001479
Airola, Michael V; Huh, Doowon; Sukomon, Nattakan et al. (2013) Architecture of the soluble receptor Aer2 indicates an in-line mechanism for PAS and HAMP domain signaling. J Mol Biol 425:886-901
Sun, Yan; Zhang, Ziwei; Grigoryants, Vladimir M et al. (2012) The internal dynamics of mini c TAR DNA probed by electron paramagnetic resonance of nitroxide spin-labels at the lower stem, the loop, and the bulge. Biochemistry 51:8530-41
Yu, Renyuan Pony; Darmon, Jonathan M; Hoyt, Jordan M et al. (2012) High-Activity Iron Catalysts for the Hydrogenation of Hindered, Unfunctionalized Alkenes. ACS Catal 2:1760-1764
Dzikovski, Boris; Tipikin, Dmitriy; Freed, Jack (2012) Conformational distributions and hydrogen bonding in gel and frozen lipid bilayers: a high frequency spin-label ESR study. J Phys Chem B 116:6694-706
Gaffney, Betty J; Bradshaw, Miles D; Frausto, Stephen D et al. (2012) Locating a lipid at the portal to the lipoxygenase active site. Biophys J 103:2134-44
Maeda, Kiminori; Lodge, Matthew T J; Harmer, Jeffrey et al. (2012) Electron tunneling in lithium-ammonia solutions probed by frequency-dependent electron spin relaxation studies. J Am Chem Soc 134:9209-18

Showing the most recent 10 out of 72 publications