This is a study of cell plasma membrane structure and functions, employing cell-vesicle interactions to probe intermembrane lipid and protein transfer and the selective translocation and sequestration of phospholipids. Energy dependent translocation of aminophospholipds has been demonstrated in human erythrocytes and platelets. The molecular properties of mechanism will be studied in intact erythrocytes and in red cell membrane preparations of progressive simplicity. Evidence for selective lipid translocation and sequestration will be sought in other cell types, including normal and transformed mammalian lymphocytes. Cell-to-vesicle protein transfer will be examined as a means of generating intact model membranes containing lymphocyte surface determinants bound in native orientation; such protein-vesicle complexes will be useful in studies of intercell recognition and fusion. Similarly, protein transfer from encapsulated mammalian viruses will be studied, with the goal of preparing liposomes targeted to cells vulnerable to viral invasion.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL023787-13
Application #
3337419
Study Section
Biophysical Chemistry Study Section (BBCB)
Project Start
1979-04-01
Project End
1993-09-29
Budget Start
1991-09-30
Budget End
1992-09-29
Support Year
13
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
Schools of Arts and Sciences
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Chen, James Y; Brunauer, Linda S; Chu, Felicia C et al. (2003) Selective amphipathic nature of chlorpromazine binding to plasma membrane bilayers. Biochim Biophys Acta 1616:95-105
Gedde, M M; Yang, E; Huestis, W H (1999) Resolution of the paradox of red cell shape changes in low and high pH. Biochim Biophys Acta 1417:246-53
Chen, J Y; Huestis, W H (1997) Role of membrane lipid distribution in chlorpromazine-induced shape change of human erythrocytes. Biochim Biophys Acta 1323:299-309
Moxness, M S; Brunauer, L S; Huestis, W H (1996) Hemoglobin oxidation products extract phospholipids from the membrane of human erythrocytes. Biochemistry 35:7181-7
Waters, S I; Sen, R; Brunauer, L S et al. (1996) Physical determinants of intermembrane protein transfer. Biochemistry 35:4002-8
Gedde, M M; Yang, E; Huestis, W H (1995) Shape response of human erythrocytes to altered cell pH. Blood 86:1595-9
Lin, S; Huestis, W H (1995) Wheat germ agglutinin stabilization of erythrocyte shape: role of bilayer balance and the membrane skeleton. Biochim Biophys Acta 1233:47-56
Brown, J W; Huestis, W H (1994) Quantification of two-dimensional NOE spectra via a combined linear and nonlinear least-squares fit. J Biomol NMR 4:645-52
Brunauer, L S; Moxness, M S; Huestis, W H (1994) Hydrogen peroxide oxidation induces the transfer of phospholipids from the membrane into the cytosol of human erythrocytes. Biochemistry 33:4527-32
Lin, S; Yang, E; Huestis, W H (1994) Relationship of phospholipid distribution to shape change in Ca(2+)-crenated and recovered human erythrocytes. Biochemistry 33:7337-44

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