Genetically Engineered Materials Science and Engineering Center, University of Washington, Seattle, WA 98195, USA.
Biopolymers. 2010;94(1):78-94. doi: 10.1002/bip.21368.
In nature, the viability of biological systems is sustained via specific interactions among the tens of thousands of proteins, the major building blocks of organisms from the simplest single-celled to the most complex multicellular species. Biomolecule-material interaction is accomplished with molecular specificity and efficiency leading to the formation of controlled structures and functions at all scales of dimensional hierarchy. Through evolution, Mother Nature developed molecular recognition by successive cycles of mutation and selection. Molecular specificity of probe-target interactions, e.g., ligand-receptor, antigen-antibody, is always based on specific peptide molecular recognition. Using biology as a guide, we can now understand, engineer, and control peptide-material interactions and exploit them as a new design tool for novel materials and systems. We adapted the protocols of combinatorially designed peptide libraries, via both cell surface or phage display methods; using these we select short peptides with specificity to a variety of practical materials. These genetically engineered peptides for inorganics (GEPI) are then studied experimentally to establish their binding kinetics and surface stability. The bound peptide structure and conformations are interrogated both experimentally and via modeling, and self-assembly characteristics are tested via atomic force microscopy. We further engineer the peptide binding and assembly characteristics using a computational biomimetics approach where bioinformatics based peptide-sequence similarity analysis is developed to design higher generation function-specific peptides. The molecular biomimetic approach opens up new avenues for the design and utilization of multifunctional molecular systems in a wide-range of applications from tissue engineering, disease diagnostics, and therapeutics to various areas of nanotechnology where integration is required among inorganic, organic and biological materials. Here, we describe lessons from biology with examples of protein-mediated functional biological materials, explain how novel peptides can be designed with specific affinity to inorganic solids using evolutionary engineering approaches, give examples of their potential utilizations in technology and medicine, and, finally, provide a summary of challenges and future prospects.
在自然界中,生物系统的生存能力是通过数以万计的蛋白质之间的特定相互作用来维持的,这些蛋白质是从最简单的单细胞生物到最复杂的多细胞生物的主要组成部分。生物分子-材料相互作用是通过分子特异性和效率来实现的,从而导致在所有维度层次的结构和功能的控制形成。通过进化,大自然母亲通过连续的突变和选择循环发展了分子识别。探针-靶标相互作用的分子特异性,例如配体-受体、抗原-抗体,总是基于特定的肽分子识别。通过以生物学为指导,我们现在可以理解、设计和控制肽-材料相互作用,并将其作为新型材料和系统的新设计工具加以利用。我们通过细胞表面或噬菌体展示方法,改编了组合设计肽文库的方案;利用这些方法,我们选择了对各种实际材料具有特异性的短肽。这些用于无机物的基因工程肽(GEPI)随后通过实验进行研究,以确定其与各种实际材料的结合动力学和表面稳定性。通过实验和建模来研究结合的肽结构和构象,并通过原子力显微镜来测试自组装特性。我们进一步通过计算仿生学方法来设计肽的结合和组装特性,其中基于生物信息学的肽序列相似性分析被开发出来以设计具有更高功能特异性的肽。这种分子仿生学方法为设计和利用具有多种功能的分子系统开辟了新的途径,这些系统在从组织工程、疾病诊断和治疗到需要无机、有机和生物材料集成的各个纳米技术领域的广泛应用中都有应用。在这里,我们通过蛋白质介导的功能性生物材料的实例来描述生物学方面的经验教训,解释如何使用进化工程方法设计对无机固体具有特定亲和力的新型肽,并举例说明它们在技术和医学中的潜在应用,最后总结了挑战和未来展望。