Molecular Dynamics And Vibrational Characteristics Of Me
我的分子动力学和振动特性
基本信息
- 批准号:6542221
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:Raman spectrometry bioimaging /biomedical imaging biomedical equipment development biophysics charge coupled device camera conformation data collection methodology /evaluation image processing infrared spectrometry interferometry lipid bilayer membrane membrane lipids membrane proteins membrane structure molecular dynamics nitric oxide oxyhemoglobin protein biosynthesis protein structure vibration
项目摘要
Summary of Work: Our research efforts encompassed two general areas: (1) The modulatory effects of bilayer lipids on the structural reorganizations of integral membrane proteins, and (2) the instrumental development and applications of vibrational Raman and infrared spectroscopic imaging techniques. (1) Our interest in characterizing the effects of fluctuating lipid microdomains within biomembranes has recently focused on cluster formation within bilayer matrices comprised of lipid mono- or polyunsaturated sn-2 chain and saturated sn-1 chain assemblies. The lateral compressibility properties of these lipid microaggregates are effective in exerting a modulatory influence on induced conformational changes occurring within integral membrane proteins. In studying spectroscopically specific lipid bilayers, appropriate acyl chain deuteration allows the vibrational dynamics of each chain moiety to be monitored separately. We have continued the utilization of both Raman and infrared spectroscopic techniques, in conjunction with freeze-quenching methodologies, toward examining model bilayer systems comprised of highly unsaturated lipids, as, for example, didocosahexaenoylphosphatidylcholine, DDPC, and fully deuterated disaturated acyl chain lipids, namely, dipalmitoylphosphatidylcholine, DPPC, and disteroylphosphatidycholine, DSPC. Established order/disorder parameters pertinent to each lipid class and to each chain system were determined, as well as a quantization of the formation of lipid microclusters. An understanding of the sizes and formation of fluctuating membrane microclusters will allow us to pursue the next step in which rhodopsin, an integral membrane protein, is inserted into the bilayer and the effects of lipid microdomains on protein conformational rearrangements are examined. (2A) Considerable emphasis has been placed on enhancing our mid-infrared spectroscopic chemical imaging microscopy techniques by combining step-scan interferometry with state-of-the-art infrared sensitive two-dimensional focal plane array detectors. The integration of high performance digital imaging with noninvasive, high resolution optical spectroscopy allows a visualization of the spatial distribution of distinct chemical species in a variety of host environments. The power of the technique is also manifest in the simultaneous acquisition of an infrared spectrum for each spatial location. As an example of the utility of the infrared imaging technique in diagnostic pathology, promising results were obtained from prostate tissue sections in which the vibrational spectral signatures for control, prostatic intraepithelial neoplastic and tumor tissues exhibited demonstrable differences. With regard to the infrared imaging instrumentation, a number of enhancing features were made in the optics, as well as in detector configurations. We have developed a novel data collection technique for step-scan, microimaging spectrometers that allows large numbers of, for example, histological samples to be imaged rapidly with a high signal-to-noise ratio (SNR). We have proposed a theoretical description for the performance characteristics of infrared hyperspectral imaging systems and have also explained theoretically the quantitative effects of the acquisition parameters on the SNR. Further, the theoretical analysis is extended to Fourier transform infrared micro-imaging employing continuous scan interferometers, a new development. For data acquisition and processing protocols we have modified gain ranging theory to account for the variation of noise by incorporating a linear model for noise prediction. A "median filtered time averaging" method for effectively reducing noise in Fourier transform imaging data has been rigorously discussed and introduced. (2B) Our imaging approaches have also been extended to the visible spectral region in which reflectance spectra are obtained using a CCD detector and appropriate liquid crystal tunable filters for wavelength discrimination. This particular noninvasive reflectance unit has been used successfully in the clinic for assessing hemoglobin saturation during systemic nitric oxide (NO) inhibition and subsequent nitric oxide inhalation. These studies demonstrate that a significant decline in the percentage of oxyhemoglobin occurs in skin tissue when blood flow is reduced after inhibition of forearm NO synthesis and that there is a restoration of oxyhemoglobin toward basal values with improved blood flow during inhalation of NO. This versatile imaging approach suggests a useful, real time probe of patients with vascular disease.
工作总结:我们的研究工作包括两个主要领域:(1)双层脂质对膜蛋白结构重组的调节作用,以及(2)振动拉曼和红外光谱成像技术的仪器开发和应用。(1)我们的兴趣在表征生物膜内的波动脂质微区的影响最近集中在由脂质单或多不饱和的sn-2链和饱和的sn-1链组装体组成的双层基质内的簇形成。这些脂质微聚集体的侧向可压缩性是有效的,在施加调制的影响,诱导的构象变化内发生的整合膜蛋白。在研究光谱特定的脂质双层,适当的酰基链氘代允许每个链部分的振动动力学分别进行监测。我们已经继续利用这两个拉曼和红外光谱技术,结合冷冻淬灭方法,对检查模型双层系统组成的高度不饱和的脂质,例如,二二十二碳六烯酰磷脂酰胆碱,DDPC,和完全氘代二饱和酰基链脂质,即二棕榈酰磷脂酰胆碱,DPPC,和二硬脂酰磷脂酰胆碱,DSPC。建立有序/无序参数有关的每个脂质类和每个链系统进行了测定,以及脂质微簇的形成的量化。波动膜微簇的大小和形成的理解将使我们能够追求的下一个步骤中,视紫红质,一个完整的膜蛋白,插入到双层和脂质微结构域对蛋白质构象重排的影响进行检查。(2A)相当大的重点已经放在提高我们的中红外光谱化学成像显微镜技术相结合的步进扫描干涉与国家的最先进的红外敏感的二维焦平面阵列探测器。高性能数字成像与非侵入性、高分辨率光谱学的集成允许在各种宿主环境中可视化不同化学物质的空间分布。该技术的威力还体现在同时获取每个空间位置的红外光谱。作为红外成像技术在诊断病理学中的应用的一个例子,从前列腺组织切片中获得了有希望的结果,其中对照、前列腺上皮内肿瘤和肿瘤组织的振动光谱特征表现出明显的差异。关于红外成像仪器,在光学和探测器配置方面做了一些改进。我们已经开发了一种新的数据收集技术的步进扫描,显微成像光谱仪,允许大量的,例如,组织学样本,以高信噪比(SNR)迅速成像。对红外超光谱成像系统的性能特点进行了理论描述,并从理论上解释了采集参数对信噪比的定量影响。此外,理论分析扩展到傅里叶变换红外显微成像采用连续扫描干涉仪,一个新的发展。对于数据采集和处理协议,我们已经修改了增益范围理论,通过将线性模型用于噪声预测来考虑噪声的变化。本文详细讨论并介绍了一种有效地降低傅里叶变换成象数据中噪声的“中值滤波时间平均”方法。(2B)我们的成像方法也已扩展到可见光谱区域,其中反射光谱是使用CCD检测器和适当的液晶可调谐滤波器的波长歧视。这种特殊的非侵入性反射单元已成功地用于临床评估血红蛋白饱和度在全身一氧化氮(NO)抑制和随后的一氧化氮吸入。这些研究表明,当前臂NO合成抑制后血流减少时,皮肤组织中氧合血红蛋白的百分比显著下降,并且在吸入NO期间,随着血流的改善,氧合血红蛋白向基础值恢复。这种多功能的成像方法表明了血管疾病患者的有用的真实的时间探针。
项目成果
期刊论文数量(0)
专著数量(0)
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Ira W. Levin其他文献
Raman spectra and vibrational assignments for dipalmitoyl phosphatidylcholine and structurally related molecules.
二棕榈酰磷脂酰胆碱和结构相关分子的拉曼光谱和振动分配。
- DOI:
10.1016/0005-2760(75)90095-8 - 发表时间:
1975 - 期刊:
- 影响因子:0
- 作者:
R. C. Spiker;Ira W. Levin - 通讯作者:
Ira W. Levin
Interaction of melittin with dimyristoyl phosphatidylcholine liposomes: evidence for boundary lipid by Raman spectroscopy.
蜂毒肽与二肉豆蔻酰磷脂酰胆碱脂质体的相互作用:拉曼光谱的边界脂质证据。
- DOI:
- 发表时间:
1980 - 期刊:
- 影响因子:0
- 作者:
Francoise Lavialle;Ira W. Levin;C. Mollay - 通讯作者:
C. Mollay
Hydrocarbon chain disorder in lipid bilayers. Temperature dependent Raman spectra of 1,2-diacyl phosphatidylcholine-water gels.
脂质双层中的烃链紊乱。
- DOI:
10.1016/0005-2760(77)90137-0 - 发表时间:
1977 - 期刊:
- 影响因子:0
- 作者:
Nehama Yellin;Ira W. Levin - 通讯作者:
Ira W. Levin
High-Fidelity Raman Imaging Spectrometry: A Rapid Method Using an Acousto-Optic Tunable Filter
高保真拉曼成像光谱测定:一种使用声光可调谐滤波器的快速方法
- DOI:
10.1366/0003702924123980 - 发表时间:
1992 - 期刊:
- 影响因子:3.5
- 作者:
P. Treado;Ira W. Levin;E. Lewis - 通讯作者:
E. Lewis
Absolute infrared intensities of hydrocarbons
- DOI:
10.1007/bf00527377 - 发表时间:
1970-03-01 - 期刊:
- 影响因子:1.500
- 作者:
Thomas P. Lewis;Ira W. Levin - 通讯作者:
Ira W. Levin
Ira W. Levin的其他文献
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{{ truncateString('Ira W. Levin', 18)}}的其他基金
Molecular Dynamics/Vibrational Study Of Membrane Assembl
膜组装的分子动力学/振动研究
- 批准号:
6983700 - 财政年份:
- 资助金额:
-- - 项目类别:
Molecular Dynamics And Vibrational Characteristics Of Membrane Assemblies
膜组件的分子动力学和振动特性
- 批准号:
8349692 - 财政年份:
- 资助金额:
-- - 项目类别:
Infrared, Raman and Visible Reflectance Spectroscopic Imaging
红外、拉曼和可见光反射光谱成像
- 批准号:
7734049 - 财政年份:
- 资助金额:
-- - 项目类别:
MOLECULAR DYNAMICS AND VIBRATIONAL CHARACTERISTICS OF MEMBRANE ASSEMBLIES
膜组件的分子动力学和振动特性
- 批准号:
6289744 - 财政年份:
- 资助金额:
-- - 项目类别:
Molecular Dynamics And Vibrational Characteristics Of Membrane Assemblies
膜组件的分子动力学和振动特性
- 批准号:
7734016 - 财政年份:
- 资助金额:
-- - 项目类别:
Infrared, Raman and Visible Reflectance Spectroscopic Imaging
红外、拉曼和可见光反射光谱成像
- 批准号:
7593513 - 财政年份:
- 资助金额:
-- - 项目类别:
MOLECULAR DYNAMICS AND VIBRATIONAL CHARACTERISTICS OF MEMBRANE ASSEMBLIES
膜组件的分子动力学和振动特性
- 批准号:
6105197 - 财政年份:
- 资助金额:
-- - 项目类别: