QUANTIFYING TOPOLOGICAL TRANSITIONS IN BIOLOGICAL MEMBRANES

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 在特定蛋白质或多肽的存在下，生物膜可以自发地进行自我重组，以允许细胞内侧和细胞外侧之间的通信。为了实现这一点，自然界使用了相互作用的协同组合，如静电、氢键、疏水和几何效应。众所周知，这种相互作用对分子打孔器很重要？例如穿透细胞膜的细胞穿透肽，以及穿透细胞膜的活性抗菌剂。这些多肽的分子机制目前还不完全清楚。此外，人们还不清楚为什么细胞穿透肽可以在不杀死细胞的情况下形成毛孔，而抗菌剂形成旨在杀死细胞的毛孔。在这项建议中，我们研究了典型的抗菌肽(α？、β？和theta-防御素)和富含精氨酸的细胞穿透肽。这两个富含精氨酸的原型系统都具有潜在的翻译影响：防御素是哺乳动物两大类抗菌肽之一，细胞穿透肽在生物技术工业中被广泛用于受控药物输送。对这些多肽设计规则的基本理解将对抗菌剂和细胞穿透性多肽的设计以及软物质物理和胶体科学产生革命性的影响。

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.