Cell Membrane Simulators in Biocompatibility Testing

生物相容性测试中的细胞膜模拟器

• 批准号: 7105055
• 负责人: DAVID M YOURTEE
• 金额: $ 24.21万
• 依托单位: UNIVERSITY OF MISSOURI KANSAS CITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-15 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7105055
• 关键词: acetylcholinesterase; bioassay; biomaterial compatibility; biomechanics; biomimetics; calorimetry; cell membrane; chemical structure function; cholesterol; cytotoxicity; dental materials; electron microscopy; enzyme activity; fluorescence polarization; intermolecular interaction; membrane activity; membrane model; method development; monomer; phosphatidylcholines; quantum chemistry; spectrometry; statistics /biometry; sterol esterase; tissue /cell culture

DESCRIPTION (provided by applicant): Cell injury begins at the first level of cell defense, the membrane. Chemicals leaching from dental restoratives can damage surrounding cellular tissue by acting at membrane surfaces. This research establishes a new method missing in biocompatibility tests to measure damage by disruption of membranes essential for cell structure, organization and function. The objective will be accomplished using biomimetic cell membranes created from phospholipid vesicles. These simulators or "BioSims" will have specified phospholipid composition and enzymatic activities. Designed and standardized BioSims will be challenged with dental monomers in systematic series and the primary causes of damage at the membrane molecular level discovered through quantum mechanical - quantitative structure activity relationships (QMSAR). The technology for designing BioSims is available from the applicant internationally networked laboratories. In applying this technology as a biocompatibility test system, the specific aims for the BioSims will accomplish the following: 1) establish reproducibility of each BioSim type produced for bioassay purposes; 2) improve knowledge of cell membranes through the study of the thermodynamics of BioSims; 3) improve knowledge of dental monomer cell membrane permeability by determining their effect on the permeability of BioSims; 4) establish effects of biomaterials on membrane bound enzymes that are critical in biological homeostasis using vesicles which will be developed and standardized as Biomimetic Cell Membrane Simulators of Acetylcholinesterase and Cholesterol Esterase and 5) employ QMSARs to predict the properties of new biomaterial to remove membrane and enzymatic destructive moieties from their chemical structure. This test system is necessary due to the increasing use of toxicologically unspecified chemicals in the formulation of polymer resin substitutes for mercury amalgam. Cell culture and animal tests available omit information on the ability of biomaterials to create disturbances in membrane intermolecular linkages. An advantage of this new system is that no experimental animals will be required. The BioSim/QMSAR approach will provide specific thermodynamics and causative structure descriptors that will help explain the molecular basis of membrane injury from biomaterials. This will enable the prediction of destructive properties of untested compounds and ensure the design of new non-toxic membrane dental materials.

描述（由申请人提供）： 细胞损伤始于细胞防御的第一层，即细胞膜。从牙科清洁剂中浸出的化学物质可通过作用于膜表面而损害周围的细胞组织。这项研究建立了一种生物相容性测试中缺失的新方法，以测量细胞结构，组织和功能所必需的膜破坏造成的损伤。这一目标将使用从磷脂囊泡产生的仿生细胞膜来实现。这些模拟器或“BioSims”将具有特定的磷脂成分和酶活性。设计和标准化的BioSims将在系统系列中接受牙科单体的挑战，并通过量子力学-定量结构活性关系（QMSAR）发现膜分子水平上损伤的主要原因。BioSims的设计技术可从申请人的国际网络实验室获得。在将该技术作为生物相容性测试系统应用时，BioSims的具体目标将实现以下目标：1）建立用于生物测定目的的每种BioSim类型的再现性; 2）通过研究BioSims的热力学来提高细胞膜的知识; 3）通过确定其对BioSims渗透性的影响来提高牙科单体细胞膜渗透性的知识; 4）使用将被开发和标准化为乙酰胆碱酯酶和胆固醇酯酶的仿生细胞膜模拟物的囊泡来确定生物材料对膜结合酶的影响，所述膜结合酶在生物体内平衡中是关键的，以及5）使用QMSAR来预测新生物材料的性质以从其化学结构中去除膜和酶破坏性部分。由于在汞合金的聚合物树脂替代品的配方中越来越多地使用毒理学上未指明的化学品，该测试系统是必要的。现有的细胞培养和动物试验忽略了生物材料对膜分子间连接产生干扰的能力。这种新系统的优点是不需要实验动物。BioSim/QMSAR方法将提供特定的热力学和因果结构描述符，这将有助于解释生物材料膜损伤的分子基础。这将能够预测未经测试的化合物的破坏性，并确保新的无毒膜牙科材料的设计。