Biomimetic Modular Design for Advanced Biomaterials

描述(由申请人提供)：拟议的研究调查仿生模块化聚合物设计作为实现先进生物材料的新策略。这项研究的广泛、长期的目标是开发具有高阶结构的生物材料的合理设计，以实现先进的性能。生物材料研究中的一个特殊挑战是设计一种具有机械强度、断裂韧性和弹性的聚合物-这三种基本机械性能在聚合物材料中是非常需要的，但通常是彼此独有的。许多结构生物聚合物，如肌肉蛋白titin，使用模块化结构域结构来实现这三个基本力学性能的组合在一个系统中。我们建议在合成生物材料中模拟模块化的结构域设计。具体地说，我们建议合成和研究具有以下模块的仿生模块聚合物：(1)四重氢键模块，(2)仿肽β-折叠模块，和(3)小蛋白模块。我们的假设是，将定义明确的模块化结构域结构引入合成生物聚合物中，应该会导致具有机械强度、韧性和弹性的生物材料。虽然这种类型的生物材料可以预见到许多生物医学应用，但这项建议集中在开发具有模块化结构域结构的模型聚合物，用来研究合成生物材料中的基本结构-性能相关性。通过拟议的研究，将实现以下具体目标：(1)利用定义明确的四氢键模块合成和研究离散低聚物和聚合物；(2)合成和研究含有模拟多肽a-Sheet模块的离散低聚物和聚合物；(3)以蛋白G结构域III(PG3)为模块合成和研究离散低聚物和聚合物；以及(4)在单分子、纳米和宏观水平上系统地研究离散低聚物以及由上述模块制备的高质量聚合物的力学性能。

DESCRIPTION (provided by applicant): The proposed research investigates a biomimetic modular polymer design as a new strategy to achieve advanced biomaterials. The broad, long-term objective of this research is to develop rational design of biomaterials having high order structures for advanced properties. A specific challenge in biomaterials research is to design a polymer that has a combination of mechanical strength, fracture toughness, and elasticity - three fundamental mechanical properties that are highly desired but usually exclusive to each other in polymeric materials. Many structural biopolymers, such as the muscle protein titin, employ modular domain structures to achieve the combination of these three fundamental mechanical properties in one system. We propose to mimic the modular domain design in synthetic biomaterials. Specifically, we propose to synthesize and investigate biomimetic modular polymers having the following modules: (1) quadruple hydrogen bonding modules, (2) peptidomimetic beta-sheet modules, and (3) small protein modules. Our hypothesis is that the introduction of well-defined modular domain structures into synthetic biopolymers should lead to biomaterials having a combination of mechanical strength, toughness, and elasticity. Whereas numerous biomedical applications can be envisioned for this type of biomaterial, this proposal is focused on developing model polymers having modular domain structures with which to study the fundamental structure-property correlation in synthetic biomaterials. Through the proposed studies the following specific aims will be accomplished: (1) Synthesis and studies on discrete oligomers and polymers using well defined quadruple hydrogen bonding modules; (2) Synthesis and studies on discrete oligomers and polymers containing peptidomimetic a-sheet modules; (3) Synthesis and studies on discrete oligomers and polymers using protein G domain III (PG3) as module; and (4) Systematic investigation on the mechanical properties of the discrete oligomers as well as the high mass polymers made from the above modules at single-molecule, nanoscopic and macroscopic levels.