Controlling Microscale Collagen Peptide Assembly with Metal Triggers

胶原蛋白是细胞外基质的主要结构蛋白之一，被发现与皮肤、骨骼、肌腱、韧带和血管有关。因此，人们对胶原蛋白在再生医学和组织工程中的应用非常感兴趣。然而，由于难以在纳米和微观尺度上精确控制蛋白质的结构，并且修改其化学结构的能力有限，天然胶原蛋白在这些应用中存在局限性。这些困难可以通过使用合成的胶原蛋白片段（多肽）作为更大的功能性生物材料的构建块来克服。为此，Chmielewski团队设计了胶原蛋白肽构建块，可以使用金属离子/配体相互作用来组装，以产生独特的微米级结构，如纤维、球体、网格和圆盘。本研究的总体目标是了解胶原蛋白肽组件形成的机制，并根据需要充分优化生成不同胶原蛋白肽微结构所需的条件。将解决的具体问题包括：(1)金属配体组合和胶原构建块的化学结构在纳米到微尺度结构的组装中起什么作用？(2)胶原肽微结构的形成机制是什么？(3)能否结合不同积木设计策略的特点，创建模块化微结构？利用金属配体相互作用组装胶原肽的初步设计提供了迷人的微结构，其中一些是前所未有的大小和形状。所提议的研究的智力价值集中在获得对装配过程的参数和机制的坚定理解上。金属促进的胶原肽组装成微尺度材料是令人回味的，并可能在许多科学领域产生广泛的影响，包括生物纳米技术，组织工程和药物输送。因此，提出的科学问题的结果将对社会产生广泛的影响，对参与这一跨学科研究领域的学生的培训也是如此。

Controlling Microscale Collagen Peptide Self Assembly with Metal TriggersCollagen is one of the major structural proteins of the extracellular matrix and is found associated with skin, bone, tendons, ligaments, and blood vessels. As such, there is great interest in using collagen for applications in regenerative medicine and tissue engineering. Natural collagen has limitations, however, for these applications due to difficulties in precisely controlling the protein's structure at the nano- and micro-scale and a limited ability to modify its chemical structure. These difficulties could be overcome by using synthetic fragments of collagen (peptides) as building blocks for larger, functional biomaterials. To this end, the Chmielewski group has designed collagen peptide building blocks that can be assembled using metal ion/ligand interactions to generate unique micron-scaled structures, such as fibers, spheres, meshes and disks.The overall goals of the proposed research are to understand the mechanism used in the formation of the collagen peptide assemblies and to fully optimize the conditions needed to generate distinct collagen peptide microstructures on demand. Specific questions that will be addressed include: (1) What roles do the metal-ligand combination and the chemical structure of the collagen building block play in the assembly of nano- to micro-scaled structures? (2) What is the mechanism of the formation of the collagen peptide microstructures? (3) Can features of different building block design strategies be combined to create modular microstructures?The initial designs of collagen peptide assembly using metal-ligand interactions have provided fascinating microstructures, some of unprecedented sizes and shape. The intellectual merit of the proposed studies is focused on gaining a firm understanding of the parameters and mechanisms of the assembly process. The metal-promoted assembly of collagen peptides into micro-scale materials is evocative and may have broad impact on many areas of science, including bio-nanotechnology, tissue engineering and drug delivery. The results of the proposed scientific questions will, therefore, have a broad impact on society, as will the training of the students who participate in this interdisciplinary area of research.