2016-02-192024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/680514摘要：膠原蛋白分子是人體中極為重要的基本建築材料，膠原蛋白分子佔人體中蛋白質的三分之一，提供人體中許多組織所需的彈性與強度，如：皮膚、肌腱、角膜、骨骼皆由膠原蛋白所組成。近年來，隨著各方面實驗與計算領域的進步，使我們能更進一步的研究這些材料的微觀結構與特性;本研究以膠原蛋白纖維為主要議題，從原子尺度出發，考慮膠原蛋白分子的胺基酸序列，建立準確描述微膠原纖維結構與性質的原子尺度模型，並進一部開發適用的多尺度計算方法，利用開發出的計算方法研究膠原蛋白組成的組織(如骨骼、肌腱)之力學性質與破壞特性，本研究將與美國的實驗團隊合作，結合實驗數據與多尺度計算方法，一方面探討與膠原蛋白相關之疾病(如成骨不全症)與ageing機制，另一方面藉由對膠原纖維微觀結構的了解，學習大自然如何利用微觀結構的設計提升材料的力學性質，促進創新仿生材料的發展。 <br> Abstract: Collagen constitutes one third of the human proteome, providing mechanical stability, elasticity and strength to connective tissues. Collagen is also the dominating material in the extracellular matrix (ECM) and is thus crucial for cell differentiation, growth and pathology. However, fundamental questions remain with respect to the origin of the unique mechanical properties of collagenous tissues, and in particular its stiffness, extensibility and nonlinear mechanical response. Although it is known that the mechanical properties of these tissues are determined by their hierarchical structure, the relation between the structure and the overall mechanical features and how each hierarchical level contributes to the tissue properties is still not established. The understanding of collagen diseases like osteognesis imperfecta is still unclear. Normal type I collagen is a heterotrimer and consists of two alpha-1 chains and one alpha-2 chain. A mouse model of the genetic brittle bone disease, osteogenesis imperfect (oim), is characterized by a replacement of the alpha-2 chain by a alpha-1 chain, resulting in a homotrimer collagen molecule. Experimental studies of oim mice tendon and bone have shown reduced mechanical strength compared to normal mice. How the molecular mutation affects the packing of collagen molecules at the microfibril level and the relationship between the molecular content and the decrease in strength is, however, still not clear. In this study, we will use a bottom-up molecular simulations and coarse grained computational modeling to study the structural and mechanical differences between the normal and oim collagen. Together with an international collaboration with experimental group in the United States, we aim to identify the molecular insights into the brittle bone disease. This project will not only help us to understand the toughening mechanisms that act both at the molecular level and at much larger dimensions but also enable the design of novel composite materials through the design of bio-inspired hierarchical structure.多尺度計算分子動力模擬膠原蛋白生物力學微觀結構collagenmulti-scale modelingbonemutationbiomechanics