Collaborative Research: Lipid Bilayers and Membrane Active Peptides

非技术性：该奖项下的工作将揭示pH触发和pH不敏感肽的序列和结构的基本原理，这些肽会导致膜的大分子大小的不稳定，从而允许低浓度的大分子通过。目前缺乏这方面的基础知识，这是设计具有广泛适用性的膜活性肽的一个障碍。通过这项工作获得的基础知识将是膜活性肽领域的重大进展。该奖项将在这里研究的活动，大分子大小的孔的形成，迄今尚未探索，其基本原理和作用机制是未知的。然而，它在生物技术和医学方面有许多潜在的应用。这项工作的成功可能使合理的设计和制备膜活性肽的药物输送和生物传感，以及癌症治疗，抗病毒和抗菌治疗，并在农业中的控制和有效释放的杀虫剂和杀真菌剂在非常低的剂量。 拟议的研究和外展活动将促进对科学的兴趣，交流知识，并在不同学科的不同层次的学生和研究人员之间建立协同互动。技术：该项目的目标是表征使大分子能够绕过质膜屏障的肽。由三名研究人员，一名工程师，一名物理学家和一名生物化学家共同努力，将描绘两个肽家族的序列-结构-功能关系，这些肽家族在低浓度下在双层中形成大的大分子大小的孔，其中一个仅在pH小于6.0时才被触发。虽然这种行为非常罕见，或者在自然界中可能不存在，但研究人员通过高通量筛选发现了具有这些特性的肽。通过比较这些肽的序列、功能和结构，他们将揭示这些家族独特活性背后的基本原理。研究人员将通过圆二色谱、荧光和原子力显微镜测量来表征pH不敏感和pH敏感的成孔剂对大分子的透化作用。 他们将学习脂双层的物理性质如何影响两类肽的功能，并将测试序列变异的特定机制假设。这项工作将为研究生、本科生和高中生提供许多研究和推广机会，启动许多新的科学职业。该奖项由物理和数学科学理事会材料研究部的生物材料计划（管理计划）颁发，由生物科学理事会分子和细胞生物科学部的分子生物物理学集群共同资助。

Non-Technical:The work under this award will reveal the fundamental principles of sequence and structure for pH-triggered and pH-insensitive peptides that cause macromolecule-sized destabilization of membranes, allowing passage of macromolecules at very low concentrations. This basic knowledge is currently lacking, and is a roadblock in the design of membrane-active peptides with broad applicability. The basic knowledge that will be gained through this work will be a significant advancement in the field of membrane-active peptides. The activity that will be studied here with this award, macromolecular-sized pore formation, has not been explored thus far and its fundamental principles and mechanism of actions are unknown. Yet, it has many potential applications in biotechnology and medicine. Success in this work may enable the rational design and preparation of membrane active peptides for drug delivery and biosensing, as well as for cancer therapies, anti-viral and anti-bacterial treatments, and in agriculture for the controlled and effective release of insecticides and fungicides at very low doses. The proposed research and outreach activities will promote interest in science, exchange of knowledge, and create synergistic interactions between students and researchers at different levels in different disciplines. Technical:The goal of this project is to characterize peptides that enable macromolecules to bypass the barrier of the plasma membrane. This collaborative effort by three investigators, an engineer, a physicist and a biochemist, will delineate the sequence-structure-function relationships of two families of peptides that form large macromolecule-sized pores in bilayers at low concentrations, one of which is triggered to act only at pH less than 6.0. While such behavior is extremely rare, or perhaps non-existent in nature, the investigators have discovered, by high-throughput screening, peptides with these properties. By comparing the sequences, functions and structures of these peptides, they will uncover the fundamental principles behind the unique activity of these families. The researchers will characterize the macromolecular permeabilization by pH-insensitive and pH sensitive pore formers by performing circular dichroism, fluorescence, and atomic force microscopy measurements. They will learn how the physical properties of the lipid bilayer affect the function of the two classes of peptides, and will test specific mechanistic hypotheses with sequence variations. The work will provide many research and outreach opportunities for graduate, undergraduate and high school students, launching many new careers in science. This award by the Biomaterials Program of the Division of Materials Research in the Directorate for Physical and Mathematical Sciences (the managing program), is co-funded by the Molecular Biophysics Cluster of the Molecular and Cellular Biosciences Division in the Directorate for Biological Sciences.