This proposal continues and expands current research in the general area of the bio-organic chemistry of lipids with heavy emphasis on understanding the behavior of giant vesicles. Giant vesicles are cell- sized structures composed of natural or synthetic lipid bilayers. Preliminary experiments have shown the occurrence of """"""""cytomimetic"""""""" events (e.g. fusion, fission, endocytosis, budding, aggregation, birthing, and wound healing) when giant vesicles are subjected to specific chemical or physical perturbations. Since these cell-like processes can be visualized by phase-contrast microscopy an opportunity now exists of directly monitoring their time-course and mechanisms. Giant vesicles have a distinct advantage over living cell membrane in that the former allows a controllable composition and morphology. Thus, one can systematically vary giant vesicles via their cholesterol content, type of phospholipid or phospholipid mixture, presence of a fusogenic agent, electric charge, etc. By this means membrane alterations can be related to molecular structure. This information is important to a variety of topics of bio-medical concern including liposomal drug delivery; endocytosis of DNA in transfection processes; transmembrane signaling by hormones; adhesion of cancer cells, platelets, etc.; fusion of viral membranes with plasma membrane; and fertilization. Specific on-going or planned experiments include: measure the rotational rate of adhered vesicles; study vesicle adhesion to cancer cells mediated by a synthetic mannose phosphonate/cholesterol conjugate; assess the fusogenic ability of phosphatidylethanol, gemini surfactants, and polymeric systems; use """"""""light intensity distributions"""""""" to monitor membrane layering; determine the rate of membrane healing after physical injury; take advantage of volume and surface area measurements to track the fate of lipid during birthing and fusion processes; and examine vesicle/cell interchange of lipid by epifluorescent microscopy.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37GM021457-31
Application #
7283230
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Program Officer
Fabian, Miles
Project Start
1977-12-01
Project End
2009-08-31
Budget Start
2007-09-01
Budget End
2009-08-31
Support Year
31
Fiscal Year
2007
Total Cost
$290,143
Indirect Cost
Name
Emory University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Yaroslavov, Alexander A; Sybachin, Andrei V; Schrinner, Marc et al. (2010) Liposomes remain intact when complexed with polycationic brushes. J Am Chem Soc 132:5948-9
Menger, Fredric M; Shi, Lei; Rizvi, Syed A A (2009) Re-evaluating the Gibbs analysis of surface tension at the air/water interface. J Am Chem Soc 131:10380-1
Yaroslavov, Alexander A; Sitnikova, Tatiana A; Rakhnyanskaya, Anna A et al. (2009) Biomembrane sensitivity to structural changes in bound polymers. J Am Chem Soc 131:1666-7
Menger, Fredric M; Shi, Lei (2009) Electrostatic binding among equilibrating 2-D and 3-D self-assemblies. J Am Chem Soc 131:6672-3
Sybachin, A V; Efimova, A A; Litmanovich, E A et al. (2007) Complexation of polycations to anionic liposomes: composition and structure of the interfacial complexes. Langmuir 23:10034-9
Yaroslavov, A A; Udalykh OYu; Melik-Nubarov, N S et al. (2001) Conventional and gemini surfactants embedded within bilayer membranes: contrasting behavior. Chemistry 7:4835-43
Yaroslavov, A A; Sukhishvili, S A; Obolsky, O L et al. (1996) DNA affinity to biological membranes is enhanced due to complexation with hydrophobized polycation. FEBS Lett 384:177-80
Menger, F M; Guo, Y; Lee, A S (1994) Synthesis of a lipid/peptide/drug conjugate: N4-(acylpeptidyl)-ara-C. Bioconjug Chem 5:162-6
Epand, R M; Epand, R F; Leon, B T et al. (1991) Evidence for the regulation of the activity of protein kinase C through changes in membrane properties. Biosci Rep 11:59-64
Charp, P A; Zhou, Q Z; Wood Jr, M G et al. (1988) Synthetic branched-chain analogues of distearoylphosphatidylcholine: structure-activity relationship in inhibiting and activating protein kinase C. Biochemistry 27:4607-12

Showing the most recent 10 out of 11 publications