Mesoscale Structural Control in 2D Peptide Assemblies

介观尺度(约100-1000 nm)高于纳米尺度，即分子和大分子(聚合物)适合的尺度，但低于日常物品的宏观尺度。在介观尺度范围内构造确定的结构是一个具有重大科学和技术意义的问题，因为它是最终实现“自下而上”制造的关键。这一过程使用结构和功能定义的纳米级构建块来创建定义了大小、组成、图案和形态的中尺度对象，这些对象反过来又代表了创建包括传感器、执行器和换能器在内的功能设备的理想平台。然而，在实践中，在介观尺度上构建合成材料的物理原理并没有得到很好的发展。相比之下，生物系统，例如细胞，将多个纳米级组件组装成定义精致、功能复杂的中尺度机器。埃默里大学文森特·康蒂塞洛教授的实验室里的研究人员正在开发从生物系统研究中衍生出来的原理，以从合成肽创建结构均质的中尺度2D组件。这些原理可推广到软材料领域。结构上定义的2D组件代表用于创建功能设备的原型。作为埃默里大学化学系本科课程改革的一部分，该项目的概念和原则正被用于开发一门新课程。改革强调使用混合教学方法将传统学科融入主题。这门新的入门课程侧重于大分子结构和功能，这是一个在本科生水平上很少涉及的主题。生命系统中存在的二维晶体或准晶体蛋白质组件展示了一系列基本的生化功能，包括作为分子筛和屏障材料、光化学能量转换器、选择性转运体以及信号转导和放大试剂。天然蛋白质组装体为合成2D蛋白质阵列中可能编码的关键功能类型提供了灵感，如果它们的结构可以跨长度尺度控制的话。这项提案研究了从合成肽创建结构定义的和可编程的中尺度2D组件的方法。多肽为2D组件的受控制造提供了许多优势；最重要的是，多肽的序列特异性使分级顺序的分子水平编程成为可能，并增强了合理控制组装的能力。然而，到目前为止，中尺度结构控制一直是偶然的，而且在合成肽的组装中观察到了这种广泛的结构多态。康蒂塞洛实验室的研究人员正在定义控制组装机制的方法，并确定促进中尺度结构有序的条件。目前正在研究三种互补的方法：(1)“活的”超分子组装体的受控成核；(2)异构体组装体的选择性形成；(3)基于几何受挫的原理的实施。这些实践中的每一种都有可能产生结构均一的中尺度2D多肽组件，这些组件反过来作为设备中使用的各种功能2D材料的结构原型。因此，这项工作解决了“中尺度挑战”中隐含的机会。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The meso-scale (circa 100-1000 nm) is above the nano-scale, in which molecules and macromolecules (polymers) fit, but below of the macroscale of everyday objects. The construction of defined structures within the meso-scale range is a problem of significant scientific and technological interest because it is key to the ultimate realization of "bottom-up" fabrication. This process employs structurally- and functionally-defined nano-scale building blocks for the creation of meso-scale objects of defined size, composition, pattern, and morphology, which in turn represent ideal platforms for the creation of functional devices including sensors, actuators, and tranducers. However, the physical principles for construction of synthetic materials on the meso-scale are not well developed in practice. In contrast, biological systems, e.g., cells, assemble multiple nano-scale components into exquisitely-defined, functionally-complex meso-scale machines. Researchers in the laboratory of Prof. Vincent Conticello at Emory University are developing principles derived from the study of biological systems to create structurally-homogeneous, meso-scale 2D assemblies from synthetic peptides. These principles are generalizable to the field of soft materials. The structurally-defined 2D assemblies represent prototypes for the creation of functional devices. Concepts and principles from this project are being utilized in the development of a new course as part of the undergraduate curriculum reform in the Department of Chemistry at Emory University. The reform emphasizes the integration of traditional disciplines into themes using a blended pedagogical approach. The new introductory course focuses on macromolecular structure and function, which is a topic rarely covered at the undergraduate level.Two-dimensional crystalline or quasi-crystalline protein assemblies present in living systems display a range of essential biochemical functions including as molecular sieves and barrier materials, photochemical energy transducers, selective transporters, and signal transduction and amplification agents. The native protein assemblies provide inspiration for the types of critical functions that could potentially be encoded within synthetic 2D protein arrays, if their structure could be controlled across length-scales. This proposal investigates methods to create structurally-defined and programmable meso-scale 2D assemblies from synthetic peptides. Peptides offer a number of advantages for the controlled fabrication of 2D assemblies; most importantly, the sequence-specificity of peptides makes possible molecular-level programming of hierarchical order and enhances the capacity for rational control of the assembly . However, thus far meso-scale structural control has been fortuitous and, this far extensive structural polymorphism was observed for assemblies of synthetic peptide. Researchers in the Conticello laboratory are defining methods to control the mechanism of assembly and identify conditions that promote meso-scale structural order. Three complementary approaches are being investigated: (1) controlled nucleation of "living" supramolecular assemblies, (2) selective formation of heteromeric assemblies, and (3) implementation of principles based on geometrical frustration. Each of these practices has the potential to generate structurally-homogeneous meso-scale 2D peptide assemblies, which in turn serve as structural prototypes for the types of functional 2D materials employed in devices. Hence this work addresses the opportunity implicit in the "meso-scale challenge".This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.