Design of Programmable, Self-Assembling Collagen Biomaterials

可编程自组装胶原生物材料的设计

• 批准号: 0907273
• 负责人: Vikas Nanda
• 金额: $ 40.5万
• 依托单位: Rutgers, The State University of New Jersey-RBHS-Robert Wood
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0907273&HistoricalAwards=false
• 关键词: Design; Programmable; Self; Assembling; Collagen

This award by the Biomaterials program in the Division of Materials Research to Robert Wood Johnson Medical School in NJ is to test the hypothesis that current computational protein design methods are adaptable to the creation of novel biomaterials based on fibrous proteins such as collagen. Natural collagens serve as inspiration for biomaterials design, assuming a multitude of structural forms ranging from thick fibrous bundles to mesh-like networks. The challenge is approached in two stages: (1) develop a 'parts list' of peptide modules that assemble into collagen triple-helices with programmable stability and specificity; and (2) link these modules together to form higher-order structures such as fibrils, networks or dendrimers. The amino acid sequences of three peptides: A, B and C have been computationally designed to specifically assemble into a triple-helix with 1:1:1 stoichiometry. Initial structural and thermodynamic characterization of peptide mixtures indicates significant progress towards this goal. Assays will be developed to precisely probe the mode of association of peptide mixtures. Experimental outcomes will be used to revise the computational design protocol. Connecting modules that orthogonally assemble with flexible linkers may lead to higher-order assemblies such as fibrils, meshes and dendrimers. A set of designs that combine orthogonal modules will be constructed and tested for types of nanostructures formed. Insight from these designs will improve the basic understanding of molecular forces in fibrous protein folding and structure. It will also promote the discovery of new collagen assemblies beyond those found in nature. A rational design framework will be essential to advance the future development of sophisticated, functional biomaterials for real-world applications.Computer simulations are being used to design synthetic proteins with applications as biosensors, therapeutics or novel enzymes. This study targets collagens - long, rope-like proteins that provide most tissues in our body from bones to skin with strength and flexibility. Using a software platform that incorporates basic physical principles of protein structure and folding, novel collagen-like peptides will be designed that self-assemble into nano-structures. The challenge is approached in two stages: (1) develop a ?parts list? of peptide modules that assemble into collagen triple-helices with programmable stability and specificity, and (2) link these modules together to form higher-order structures such as fibrils, networks or dendrimers. These compounds will be valuable as tissue engineering substrates and biomaterials

材料研究部的生物材料项目授予新泽西州罗伯特·伍德约翰逊医学院的这一奖项是为了验证一个假设，即目前的计算蛋白质设计方法适用于基于纤维蛋白质（如胶原蛋白）的新型生物材料的创造。天然胶原蛋白是生物材料设计的灵感来源，具有多种结构形式，从厚纤维束到网状网络。 该挑战分两个阶段进行：（1）开发肽模块的“部件列表”，这些肽模块组装成具有可编程稳定性和特异性的胶原蛋白三螺旋;以及（2）将这些模块连接在一起以形成更高级的结构，如原纤维，网络或树枝状聚合物。 三种肽：A、B和C的氨基酸序列已经通过计算设计成以1：1：1化学计量特异性地组装成三螺旋。 肽混合物的初始结构和热力学表征表明朝着这一目标取得了重大进展。将开发测定以精确探测肽混合物的缔合模式。 实验结果将用于修改计算设计方案。 与柔性接头正交组装的连接模块可以导致更高阶的组装，例如原纤维、网状物和树枝状聚合物。 将构建一组结合联合收割机正交模块的设计，并测试所形成的纳米结构的类型。 从这些设计的见解将提高纤维蛋白质折叠和结构的分子力的基本理解。 它还将促进新的胶原蛋白组装体的发现，而不是在自然界中发现的。 一个合理的设计框架将是必不可少的，以推动未来的发展，复杂的，功能性的生物材料的实际应用。计算机模拟正在被用来设计合成蛋白质与生物传感器，治疗或新的酶的应用。 这项研究的目标是胶原蛋白-长，绳状蛋白质，提供我们身体中的大多数组织，从骨骼到皮肤的强度和灵活性。 使用一个软件平台，结合蛋白质结构和折叠的基本物理原理，新的胶原蛋白样肽将被设计成自组装成纳米结构。 的挑战是接近两个阶段：（1）开发一个？零件清单？肽模块组装成具有可编程稳定性和特异性的胶原蛋白三螺旋，以及（2）将这些模块连接在一起以形成更高级的结构，如原纤维、网络或树枝状聚合物。 这类化合物作为组织工程基质和生物材料具有重要的应用价值