药物与生物膜相互作用的近代生物物理方法研究进展

作者研究发现多不饱和脂肪酸、胆固醇、磷脂是构成生化抗癌药物的重要因素，三者只有按一定的比例制成类似生物膜的液晶态脂体，才能发挥各自的作用。在此基础上，提出了生物液晶态模型．根据该模型设计、研制了新型的抗癌药物——亚油酸铀免疫定向脂质体。初步研究表明：该药物有明显的抗肿瘤作用，进而阐明了近代生物物理技术在研究液晶态生特膜与癌症在其治疗之间关系中的重要作用。     

在气/液界面牛血清蛋白对阴离子磷脂DPPG脂单层膜的动态行为和形貌变化的影响

The interaction between bovine serum albumin (BSA) and the anionic 1.2-dipalmitoyl-snglycero- 3-(phospho-rac-(1-glycerol)) (sodium salt) (DPPG) phospholipid at different subphase pH values was investigated at air-water interface through surface pressure measurements and atomic force microscopy (AFM) observation. By analyzing surface pressure-mean molecular area (π-A) isotherms, the limiting molecular area in the closed packing state-the concentration of BSA (A_lim-[BSA]) curves, the compressibility coefficient-surface pressure (C_S^-1-π) curves and the difference value of mean molecular area-the concentration of BSA (ΔA-[BSA]) curves, we obtained that the mean molecular area of DPPG monolayer became much larger when the concentration of BSA in the subphase increased at pH=3 and 5. But the isotherms had no significant change at different amount of BSA at pH=10. In addition, the amount of BSA molecules adsorbed onto the lipid monolayer reached a threshold value when [BSA]>5×10^-8 mol/L for all pHs. From the surface pressure-time (π-t) data, we obtained that desorption and adsorption processes occurred at pH=3, however, there was only desorption process occurring at pH=5 and 10. These results showed that the interaction mechanism between DPPG and BSA molecules was affected by the pH of subphase. BSA molecules were adsorbed onto the DPPG monolayers mainly through the hydrophobic interaction at pH=3 and 5, and the strength of hydrophobic interaction at pH=3 was stronger than the case of pH=5. At pH=10, a weaker hydrophobic interaction and a stronger electrostatic repulsion existed between DPPG and BSA molecules. AFM images revealed that the pH of subphase and [BSA] could affect the morphology features of the monolayers, which was consistent with these curves. The study provides an important experimental basis and theoretical support to understand the interaction between lipid and BSA at the air-water interface.     

Origin9.0软件在微波技术实验中的应用探讨

以近代物理实验中的微波技术实验为例,详细介绍了用Origin9.0软件进行绘图和非线性拟合处理实验数据的方法,对实验测定的数据进行绘图、计算、拟合。该软件的应用,能够有效避免人工计算处理所带来的误差,大大简化实验数据处理过程,获得人工绘图难以获得的更多的信息量,且运用软件结果高效准确。     

Lipid membrane: inelastic deformation of surface structure by an atomic force microscope

The stability of the 1,2-Dioleoyl-sn-Glycero-3-[phospho-rac-1-Glycerol-Na] liposome in the liquid crystalline state have been investigated using an atomic force microscope (AFM). We have observed the inelastic deformation of the sample surface. The AFM tip causes persistent deformation of the surface of the lipid membrane, in which some of the lipid molecules are eventually pushed or dragged by the AFM tip. The experiment shows how the surface structure of the lipid membrane can be created by the interaction between the AFM tip and lipid membrane. When the operating force exceeds 10^-8 N, it leads to large deformations of the surface. A square region of about 1×1μm² is created by the scanning probe on the surface. When the operating force is between 10^-11N and 10^-8N, it can image the topography of the surface of the lipid membrane. The stability of the sample is related to the concentration of the medium in which the sample is prepared.     

羧甲基茯苓多糖结构的红外光谱表征与原子力显微镜观测

用傅里叶变换红外光谱对羧甲基茯苓多糖(carboxymethylpachymaran, CMP)的结构进行了表征,用原子力显微镜(atomic force microscopy, AFM)对不同溶液环境下CMP的形态变化进行了观测。结果表明：经过羧甲基修饰,茯苓多糖在水中的溶解性显著增加,890 cm-1处的β-D-葡聚糖特征吸收峰明显减弱,1 333 cm-1处出现次甲基振动吸收峰,1 606 cm-1处出现CO非对称伸缩振动吸收峰,表明羧甲基化成功;原子力显微镜分析表明：在不同溶液条件下,CMP分子以不同形态存在,多糖溶液的浓度、离子强度及溶剂的物化特性均能对CMP的分子链构象及链间相互作用形式产生影响,推测可能与CMP分子内、分子间的氢键缔合及静电作用有关,CMP分子与云母基底间的吸附及静电作用也会对CMP的分子链构象及图像质量产生影响。     

细胞的原子力显微镜最佳成像条件研究

通过对不同处理条件和测试条件下人肝癌细胞SMMC-7721的原子力显微镜图像的分析和研究,得到了在大气环境和溶液环境中肝癌SMMC-7721细胞的最佳成像条件,同时建立了用原子力显微镜观测活细胞的实验方法.使用0.5%、1%、1.5%的戊二醛溶液固定细胞后再漂洗,变换原子力显微镜的扫描模式,调节扫描参量并在大气环境下观测以寻找该环境下的最佳成像条件;将用多聚赖氨酸处理基底后的培养细胞直接放置于生理溶液中用原子力显微镜进行溶液环境观测,比较扫描时限并分别改变环境液体类型、探针以及扫描频率,比较了不同条件下原子力显微镜图像的差异,在得出最优参量的同时对其相关原理进行了分析,建立了活细胞实时观测的实验方法.比较两种条件下的细胞图像发现,戊二醛溶液固定过的细胞与生理溶液环境中的活细胞有很大差别,在生理溶液条件下的细胞饱满,可见到光滑清晰的细胞边缘;但戊二醛溶液固定的细胞表面粗糙,细胞边缘不清晰,表明固定后观测到的细胞与生理状态下活细胞的表面形貌存在很大差异.     

脂双层膜表面结构与稳定性的原子力显微镜研究

用原子力显微镜研究了1,2－二油酸甘油－3－磷酸－1甘油（DOPG）脂双层膜 的表面结构与稳定性。实验结果表明,原子力显微镜的探针与脂双层膜的相互作用 导致脂双层膜表面产生一个永久的损伤。静电相互作用对脂双层膜结构和稳定性的 影响表明,在NaCl溶液中制成的脂质体,随着NaCl浓度的增加,它们的双层膜更稳 定。在低的NaCl浓度则经常被损伤,在1 mol/L NaCl溶液中制备的指双层变得更稳 定。在KCl溶液中结果恰好相反。在高的KCl浓度中经常被损伤,随着KCl浓度的降 低,它们的双层膜更稳定。葡萄糖和蔗糖对脂双层膜结构有稳定作用。     

髓鞘碱性蛋白对细胞膜脂质分子DPPC、DPPE单层膜影响机理研究

本文通过Langmuir单层膜的表面压力-平均分子面积(π-A)曲线的测定与分析,分别对髓鞘碱性蛋白(MBP)与细胞膜中不同头部基团脂质分子二棕榈酰基磷脂胆碱(DPPC)和二棕榈酰基磷脂酰乙醇胺(DPPE)在空气/液体界面上的相互作用过程进行了系统研究.实验结果表明:(1)当界面上脂质含量一定时,亚相中随着MBP浓度的增大,DPPC、DPPE单层膜的等温线向平均分子面积较大的方向移动;(2)在单层膜表面压力为10 mN/m时,一个MBP分子分别结合140±3个DPPC分子和100±3个DPPE分子,随着表面压力增大,当MBP分子分别与两种磷脂分子相互作用时,MBP插入到磷脂单层界面的个数逐渐减少;(3)随着蛋白质浓度的增加,脂分子形成的单层膜变得较为疏松,且MBP分子易于插入到分子头部较小的DPPE单层膜中;(4)蛋白质的存在使DPPC单层膜的表面压力逐渐减小,且蛋白质浓度越大表面压力降低越多,DPPC被MBP带入到亚相中越多;(5)对于DPPE单层膜,蛋白质通过与DPPE相互作用插入到界面膜中,引起表面压力增大,且蛋白质浓度越高,压力变化量越大.     

脂肪酸环己胺合铂结构及抗肿瘤作用研究

用X射线衍射、红外光谱、差热分析等对合成的几种脂肪酸环己胺铂配合物的结构进行了研究.并选用黑色素瘤(LiBr),白血病细胞K₅₆₂,肝癌(7721)细胞做抗癌活性实验.结果发现:这几种脂肪酸环己胺铂配合物对肿瘤细胞的生长有抑制作用,并与浓度梯度和脂肪酸碳链的长度密切相关.肿瘤细胞对用不同强度磁场处理的药物有不同的敏感性.随着磁场强度的增加,抗癌效果明显增强.     

开发设计性和创新性大学物理实验的尝试

增加设计性和创新性实验的开设比例, 不仅是大学物理实验课程改革需要, 更是培养大学生创新能力 的必然要求. 本文设计、 搭建了一种基于刚体转动惯量实验仪的液体粘滞系数测量实验装置, 并做了测量举例. 该 装置不仅克服了手动秒表计时误差大的缺点, 而且扩展了测量对象. 本装置的设计、 搭建可由学生利用实验室已有 设备独立完成, 适合开设设计性和创新性大学物理实验