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类型 基础研究 预答辩日期 2018-03-08
开始(开题)日期 2015-12-15 论文结束日期 2018-01-05
地点 四牌楼校区岩土工程馆西侧小白楼生物表界面实验室会议室305 论文选题来源 国家自然科学基金项目     论文字数 6.9 (万字)
题目 和频振动光谱技术的开发和应用—磷脂膜和高分子膜表界面的研究
主题词 和频振动光谱,开发,应用,磷脂膜,高分子膜
摘要 生物膜界面尤其是细胞膜界面, 它涉及到物质传输、信号传导、蛋白吸附与脱附等众多生理过程。因此,揭示细胞膜界面的生物学效应至关重要。由于细胞膜的复杂性,磷脂单分子层和磷脂双分子层常常当作模型细胞膜被广泛研究。过去几十年来,多种实验和模拟技术用于模型细胞膜的研究,例如X-射线和中子衍射、傅里叶变换红外光谱、分子动力学模拟等等。然而,这些传统的表征技术由于缺少表界面选择性,并非理想的表界面表征技术。幸运的是,和频振动光谱迅速发展起来,成为探测表界面最强有力的手段之一。其具有超高的单分子层灵敏性、高度的表界面选择性,能够实时原位地提供表界面分子结构、取向以及取向分布等信息,以上这些优点是其它表征技术所难以达到的。 本论文采用传统和相位敏感和频振动光谱技术,开展了模型细胞膜和高分子膜表界面的研究工作。首先解决了有关磷脂膜的两个重要基本问题。第一,研究了磷脂单层膜在不同接触介质(空气和水)中的分子取向结构与SFG信号强度。发现棱镜上的磷脂单层接触水面上的磷脂单层形成磷脂双分子层后,棱镜上磷脂单层的SFG信号显著增强,原因主要是由于界面菲涅尔系数增大所引起的。第二,研究了磷脂单层在不同实验几何构型(外反射和全反射)下SFG光谱特征,发现其ssp光谱是相同的,而ppp光谱是不同的。ppp光谱不同的原因在于有效二阶非线性极化率与菲涅尔系数之间的相干。这两个基本问题的解决对于理解不同接触介质和不同实验几何构型下的磷脂分子取向结构以及SFG光谱的研究具有重要意义。基于以上两个研究为基础,进而从分子水平上定量以及定性地研究了治疗阿尔茨海默型痴呆症的药物分子盐酸美金刚与磷脂双层膜的相互作用,发现盐酸美金刚与PC磷脂双层无明显相互作用;然而其与PG双层的下层有强烈的相互作用,原因是静电相互作用,使得下层磷脂分子的甲基基团倾向于平躺在界面上,经计算其平均取向角约为82°。这为更好的理解盐酸美金刚与细胞膜的相互作用机制、药代动力学以及开发用于治疗神经退行性疾病的药物分子具有潜在的重要意义。 鉴于和频振动光谱的表界面选择性和灵敏性以及高分子膜材料的广泛应用,将SFG技术进一步拓展到了高分子膜表界面的研究。研究了聚丙烯酸酯类薄膜在金属基底以及夹心在金属基底与二氧化硅基底之间的玻璃化转变温度。发现在金属基底上,Tg随着薄膜厚度的降低而降低;而薄膜夹心在金属基底与二氧化硅基底之间时,Tg随着薄膜厚度的降低反而升高。这表明无自由表面的情况下,二氧化硅与薄膜之间的相互作用对薄膜Tg有较大影响。本研究发展了一种SFG结合金属表面等离子体激元的新方法探测高分子薄膜的玻璃化转变温度。为了将SFG 技术继续向前推动一步,实现精准测量,成功搭建了共线相位敏感飞秒和频振动光谱系统,接着以聚苯乙烯薄膜为模型,采用此系统研究了其去润湿行为,发现去润湿后聚苯乙烯分子主链和链端基倾向于更加有序,且朝向空气的一侧,而侧基苯环则倾向于平躺在界面上。 总之,本论文采用世界先进的和频振动光谱技术从分子水平上定量以及定性地研究了模型细胞膜和高分子膜表界面。这有助于理解生物膜以及高分子膜的宏观性质与微观结构之间的关系,从而推动了和频振动光谱技术在软物质领域的应用与发展。
英文题目 DEVELOPMENT AND APPLICATION OF SUM FREQUENCY GENERATION VIBRATIONAL SPECTROSCOPY: STUDYING SURFACES AND INTERFACES OF PHOSPHOLIPID MEMBRANES AND PLOYMER THIN FILMS
英文主题词 sum frequency generation vibrational spectroscopy, development, application,phospholipid membrane, polymer thin film, surface and interface
英文摘要 Biomembrane interfaces, expecially cell membrance interfaces, involve many biological processes including transportation, signal transduction, absorption and desorption of protein etc. So it is very critical to reveal the biological events occurring at cell membrane interfaces. Given the complexity of real cell membranes, lipid monolayers and lipid bilayers acting as the model cell membrances were widely studied. In the past decades, many experimental and computational techniques, e.g., X-ray and neutron diffraction, Fourier transform infrared spectroscopy, and molecular dynamics simulation, have been extensively employed to investigate the model cell membrances. However, these traditional techniques are not the ideal tools to characterize surfaces and interfaces due to the lack of the sensitivity and the selectivity of surfaces and interfaces. Fortunately, Sum frequency generation (SFG) vibrational spectroscopy with inherent ultrahigh selectivity and submolecular sensitivity of surfaces and interfaces has been rapidly developed into one of the most powerful techniques for surface and interfacial characterization. SFG has the ability to get the molecular structure, orientation, and orientation distribution at surfaces and interfaces in real time and in situ, these advantages were hardly obtained by other characterization techniques. In this thesis, model cell membranes and polymer thin films were investigated using the traditional and the phase-sensitive SFG. Firstly, two significant and fundamental issues were addressed. One is concerning the change of molecular orientation and SFG signal intensity when a lipid monoayer on prism in air contacts with a lipid monolayer on water, founding that the SFG signal enhancement is mainly caused by the increscent interfical Fresnel coefficient rather than the orientation change of the lipids. The other one is about the SFG spectral features of a lipid monolayer on silica window (external reflection) and a lipid monolayer on right-angle silica prism (total internal reflection). The results showed that SFG ssp spectra were the same while SFG ppp spectra were different for these two geometries, which was attrituted to the interaction between effective second-order nonlinear susceptibilities and interfical Fresnel coefficients. The settlements of these two issues are extremely important for deep understanding of the SFG spectral features and lipid molecular structures when various contacting media and experimental geometries were employed in SFG study. Based on above studies, quantitative and qualitative analyses of the interaction between memantine (a drug for treating Alzheimer’s disease) and model cell membranes (PC bilayers and PG bilayers) were carefully performed at the molecular level, indicating memantine cannot disrupt the PC bilayer, but can dramatically interact with the distal leaflet of the PG bilayer because of the electrostatic attraction, which makes methyl groups of PG lipids in the distal leaflet tend to lie down at the interface, the average orientation angle was calculated to be around 82° with respect to the surface normal. This research is benifical to better understand the interaction mechanism between them, pharmacokinetics, and will potentially promote the development of new drugs for treating the neurodegenerative diseases. Given the surface and interfacial selectivity and sensitivity of SFG and its wide application, SFG was applied to probe surfaces and interfaces of polymer thin films. The Tgs of polyacrylates thin films supported on the metal substrate and sandwiched between metal and silica substrates were investigated. It turned out that the Tgs decrease and Tgs increase with decreasing film thickness for the supported and the sandiwiched films, respectively. This experiment demonstrated that, without free surface, the interaction between silica and polymer can significantly affect the Tgs of polymer thin films. A novel approach to detect the Tg of polymer thin films based on the metallic surface plasmon polariton and SFG was developed in this study. To continually promote the development of SFG for the accurate detection, the nonlinear phase-sensitive femtosecond SFG was successfully built up. And then using the phase-sensitive femtosecond SFG, the dewetting behaviors of polystyrene thin films serving as the model were studied, showing that main chains and end groups of polystyrene are inclined to be orderly oriented towards the air whereas side phenyl groups are prone to lie flat at the surface after dewetting. In summary, the state-of-the-art SFG was used to quantitatively and qualitatively study the model cell membranes and polymer thin films at the molecular level, which helps to understand/build up the correlation between the microscopic molecular structure and the macroscopic performance with respect to interfaces of biomembranes and polymer thin films, and thus promoting the development and application of SFG in soft mater field.
学术讨论
主办单位时间地点报告人报告主题
生物表界面实验室 2017年12月 校西生物表界面实验室三楼会议室 李柏霖 相位敏感和频振动光谱的成功搭建
生物表界面实验室 2017年9月 校西生物表界面实验室三楼会议室 李柏霖 和频振动光谱研究PS的去润湿行为
生物表界面实验室 2016年6月 校西生物表界面实验室三楼会议室 李柏霖 金表面等离子体激元对于SFG信号的增强
生物表界面实验室 2015年9月 校西生物表界面实验室三楼会议室 李柏霖 磷脂单层膜的SFG信号偏振选择性
生物表界面实验室 2017年12月 校西生物表界面实验室三楼会议室 胡鹏程 消逝波研究纳米颗粒界面
生物表界面实验室 2017年10月 校西生物表界面实验室三楼会议室 马永豪 离子对磷脂膜flip-flop行为的影响
生物表界面实验室 2016年11月 校西生物表界面实验室三楼会议室 郑国哲 丝蛋白多孔材料的三维细胞培养
生物表界面实验室 2015年12月 校西生物表界面实验室三楼会议室 李旭 聚甲基丙烯酸羟乙酯的表面水合作用
     
学术会议
会议名称时间地点本人报告本人报告题目
美国化学会 2016年8月 美国费城 Qualitative and Quantitative Analyses of the Molecular-Level Interaction between Memantine and Model Cell Membranes
中国生物医学工程联合学术年会 2015年11月 苏州 分子水平上磷脂膜界面的非线性光谱研究
东南大学生医学院 2017年10月 生物电子学国家重点实验室会议室
东南大学生医学院 2016年5月 生物电子学国家重点实验室会议室
     
代表作
论文名称
Thermo- and pH-responsive behaviors of aqueous poly(acrylic acid)/poly(4-vinylpyridine) complex mate
Interfacial Fresnel Coefficients and Molecular Structures of Model Cell Membranes: From a Lipid Mono
Method to Probe Glass Transition Temperatures of Polymer Thin Films
Qualitative and Quantitative Analyses of the Molecular-Level Interaction between Memantine and Model
Sum Frequency Generation of Interfacial Lipid Monolayers Shows Polarization Dependence on Experiment
 
答辩委员会组成信息
姓名职称导师类别工作单位是否主席备注
周东山 正高 教授 博导 南京大学
刘宏 正高 教授 博导 东南大学
周晓燕 正高 教授 博导 南京林业大学
吴富根 正高 教授 博导 东南大学
杨芳 正高 教授 博导 东南大学
      
答辩秘书信息
姓名职称工作单位备注
韩晓锋 副高 副教授 东南大学