Presidential Young Investigator Award: Membrane Science

总统青年研究员奖：膜科学

• 批准号: 9157856
• 负责人: Kimberly Anderson
• 金额: $ 26.17万
• 依托单位: University of Kentucky Research Foundation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-07-01 至 1996-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9157856&HistoricalAwards=false
• 关键词: Presidential; Young; Investigator; Award; Membrane

The encapsulation of biologically active substances into membranes has emerged as an important research area with great potential for industrial applications. These systems permit entrapped substances to be protected in vivo from inactivation or degradation and also permit delayed or controlled kinetics of release. Systems which employ naturally occurring substances as carriers, such as phospholipid vesicles and resealed erythrocyte membranes, have certain advantages with respect to biocompatibility. However, a major drawback of these carrier systems is their lack of specificity in site of delivery. If this could be solved, great strides in their use would be made. Two of the most important physical properties that can effect in vivo survival and targeting of these systems are deformability and adhesion. It has been shown that large phospholipid vesicles become entrapped in the first capillary bed reached after i.v. administration and they also have difficulty in moving from the circulation into the interstitial space. It is possible that these problems could be attributed to their lack of deformability. Intact erythrocytes are able to deform during passage through capillaries and into the interstitial space. However, it is possible that the morphology of these cells change drastically following the incorporation of molecules into the resealed erythrocyte. To date, the deformation characteristics of these systems have not been quantified. Targeting of these carriers to specific cells in vivo also depends a great deal on carrier-endothelial cell interactions during dissemination through the circulation and carrier-cell interactions following extravasation into the tissue space. These interactions are strongly dependent on the adhesion properties of the systems. Hence, it is possible that specific targeting could be accomplished by modifying the adhesion properties of the carriers. Current research is focused on the investigation of deformability and adhesion properties of both normal and genetically altered cells. The laboratory is equipped with a state-of-the-art video microscopy system that employs the micropipette aspiration technique and a microscopic flow chamber to quantify both deformation and adhesion properties of membranes, respectively. Recent results show that genetically altering normal fibroblast cells, modify membrane adhesion and deformability properties. The cells are currently being tested, using biochemical assays, to determine the adhesion molecules and structural characteristics responsible for the properties observed. During the period of the PYI award, expertise in cellular membranes will be employed to investigate adhesion, deformation and transport properties of resealed erythrocytes membranes and phospholipid vesicles with the ultimate goal of producing optimal carrier systems.

将生物活性物质包封到 膜已经成为一个重要的研究领域， 工业应用的潜力。 这些系统允许 在体内被保护免于失活的截留物质 也允许延迟或受控的动力学 释放 使用天然存在的系统 作为载体的物质，如磷脂囊泡和 重新密封的红细胞膜，具有一定的优势， 关于生物相容性。 然而， 这些载体系统的缺点是它们缺乏对 交付. 如果这个问题能得到解决， 会被制造出来。 两个最重要的物理性质 可以影响这些细胞在体内的存活和靶向 系统的主要特性是可变形性和粘附性。 已经表明 大的磷脂囊泡被包裹在第一个 静脉给药后达到毛细血管床， 很难从循环进入 间隙 这些问题有可能 这是因为它们缺乏可变形性。 完整 红细胞能够在通过 毛细血管进入细胞间隙 但据 这些细胞的形态可能会发生剧烈的变化 在将分子结合到重新密封的 红细胞。 迄今为止， 这些系统尚未量化。 靶向这些 载体在体内对特定细胞的作用也在很大程度上取决于 在传播过程中载体-内皮细胞的相互作用 通过循环和载体细胞的相互作用 在外渗到组织间隙中之后。 这些 相互作用强烈依赖于粘附特性 的系统。 因此，有可能特定的目标 可以通过改变 运营商。 目前的研究集中在调查 变形性和粘附性能的正常和 基因改变的细胞 实验室配备了一个 最先进的视频显微镜系统， 微管抽吸技术和显微流动 用于量化变形和粘附性能的试验室 膜，分别。 最近的结果显示， 基因改变正常成纤维细胞，修饰膜 粘合性和可变形性。 将细胞 目前正在测试，使用生化分析，以确定 粘附分子及其结构特征 对观察到的属性负责。 期内 在PYI奖中，细胞膜专业知识将 用于研究粘附、变形和运输 再密封红细胞膜和磷脂的性质 囊泡的最终目标是产生最佳载体 系统.