MODEL MEMBRANES DISPLAYING COEXISTING LIQUID ORDERED AND DISORDERED PHASES

显示共存液态有序相和无序相的模型膜

• 批准号: 8172113
• 负责人: ANDREW SMITH
• 金额: $ 0.29万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172113
• 关键词: Biological Models; Brain; Cell membrane; Cells; Cholesterol; Computer Retrieval of Information on Scientific Projects Database; Disease; Electron Spin Resonance Spectroscopy; Equilibrium; Funding; Grant; Institution; Life; Lipids; Liquid substance; Membrane; Methods; Modeling; Phase; Research; Research Personnel; Resources; Source; Sphingomyelins; Spin Labels; System; United States National Institutes of Health; dioleoylphosphatidylcholine; membrane model

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 为了评估细胞质膜的筏假说的有效性，我们检查了脑 - 甲状腺素蛋白（SPM） /二甲酰二酰磷脂酰磷脂胆碱（DOPC） /胆碱胆碱 /胆固醇模型模型的液体有序（LO）（LO）（LO）（LO）的动力学和平衡。 使用该脂质系统的已知相图，该脂质系统包含LO和LD阶段的一相区域与两相共存区域之间的相边界以及ESR光谱拟合方法（确定在共存膜相结合的新方法，使用Spin-sl-label Esr，Y.-W. Chiang，Y.-W. Chiang，J。Zhao，J.Wu，J.Wu，Shimane，G. Biophysica-biochimica Acta 1668，99-105,2005）从边界光谱的线性叠加中，我们通过LO+LD共存区域确定了一个Tieline。 对于该三元脂质系统，许多对LO和LD相的组合物可以在平衡处共存，因此Tielines对于木筏进行建模是必要的，因为它们告诉我们哪种相位组合共存，因此哪对组成最佳质膜膜。 如果在SPM/DOPC/胆固醇模型系统中观察到的LO和LD相在物理上与RAFT域相似，则根据ESR光谱拟合确定的模型膜中自旋探针的动态参数应与Plasmammbranes中同一探针的动态参数相似。 发现这是正确的，在迄今为止，从链条标记的自旋探头的动态参数中，迄今为止确定的一条tieline的边界组成与活细胞中相同自旋探针的动态参数进行了很好的比较（在活细胞中的同一自旋探针（在质细胞的质膜中共存结构域，由ESR Spectroscoppopy表征的活细胞中的质膜中，M.J. Swamy，M.J. Ciani，M.Geiani，M.Gea。 J.H.释放，Biophys。 对LO和LD相位平衡的更广泛分析以及模型和实际质膜之间的动态比较将需要确定LO+LD相共存区域的整个Tielines。