QUANTIFYING TOPOLOGICAL TRANSITIONS IN BIOLOGICAL MEMBRANES

量化生物膜中的拓扑转变

• 批准号: 8362400
• 负责人: GERARD C WONG
• 金额: $ 0.03万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362400
• 关键词: Arginine; Biological; Biotechnology; Cell membrane; Cells; Colloids; Communication; Defensins; Drug Delivery Systems; Electrostatics; Funding; Grant; Hydrogen Bonding; Industry; Mammals; Membrane; Molecular; National Center for Research Resources; Nature; Peptides; Physics; Principal Investigator; Proteins; Radiation; Research; Research Infrastructure; Resources; Science; Side; Source; System; United States National Institutes of Health; antimicrobial; antimicrobial peptide; cell killing; cost; design; extracellular; structural biology; theta-defensin

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. In the presence of specialized proteins or peptides, a biological membrane can spontaneously restructure itself to allow communication between the intracellular side and the extracellular side. To accomplish this, nature uses synergistic combinations of interactions, such as electrostatics, hydrogen bonding, hydrophobic, and geometric effects. Such interactions are known to be important for molecular ?hole punchers? such as cell penetrating peptides that cross cell membranes, and membrane?active antimicrobials that permeate cell membranes. The molecular mechanisms of these peptides are not fully understood at present. Moreover, it is not understood why cell penetrating peptides can form pores without killing cells, whereas antimicrobials form pores that are designed to kill cells. In this proposal, we examine prototypical antimicrobial peptides (alpha?, beta?, and theta-defensins) and arginine?rich cell penetrating peptides. Both of these arginine?rich prototypical systems have potential for translational impact: Defensins constitute one of the two main classes of antimicrobial peptides in mammals, and cell penetrating peptides are used broadly for controlled drug delivery in the biotechnology industry. A fundamental understanding of design rules governing these peptides will have a transformative impact in the design of antimicrobials and cell penetrating peptides, as well as soft matter physics and colloid science.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 在特定蛋白质或肽的存在下，生物膜可以自发地重组自身以允许细胞内侧和细胞外侧之间的通信。为了实现这一点，自然界使用相互作用的协同组合，如静电，氢键，疏水和几何效应。这种相互作用是已知的重要分子？打孔器？例如穿过细胞膜的细胞穿透肽，膜？渗透细胞膜的活性抗菌剂。这些肽的分子机制目前还不完全清楚。此外，尚不理解为什么细胞穿透肽可以形成孔而不杀死细胞，而抗菌剂形成的孔被设计为杀死细胞。在这个提议中，我们研究了原型抗菌肽（α？，贝塔？和θ-防御素）和精氨酸？富含细胞穿透肽。这两种精氨酸？丰富的原型系统具有潜在的翻译影响：防御素构成哺乳动物中两大类抗微生物肽之一，细胞穿透肽广泛用于生物技术工业中的受控药物递送。对这些肽的设计规则的基本理解将对抗菌剂和细胞穿透肽的设计以及软物质物理学和胶体科学产生变革性的影响。