Huang Jia, Cebe Peggy, Kaplan David L
Department of Chemical and Biological Engineering, Tufts University, Medford, Massachusetts, 02155 USA.
Macromol Rapid Commun. 2009 Feb 18;30(4-5):336-44. doi: 10.1002/marc.200800591. Epub 2009 Jan 22.
Collagen type I peptides, representative of native to disease states for the bone disease, Osteogenesis imperfecta, were studied with regard to self-assembly into triple helices and liquid crystalline mesophases. The purpose of the study was to establish insight into collagen mutations in terms of propagation of single chain defects up the scale of materials hierarchy, toward solid state fibril assemblies formed from collagen. Studies carried out in vitro demonstrated the value of this approach in establishing in vitro disease models, as the degree of collagen disruption could be recapitulated by the point mutations to show major impact on macroscopic features. Fourier transform infrared spectroscopy, circular dichroism, atomic force microscopy and optical ellipsometry were used to assess the structural and morphological changes at the various length scales post assembly. The results demonstrated that glycine to alanine to aspartic acid single substitutions in the collagen peptides progressively disrupted normal assembly, reflected in lower thermal stability, loss of triple helical structure and loss of mesophase formation. This approach can provide a basis upon which to study collagen biomaterial templates for controlled hydroxyapatite formation and changes in cell signaling related to bone remodeling, related to the severity of the disease.
针对代表骨病成骨不全症从天然状态到疾病状态的I型胶原蛋白肽，研究了其自组装成三螺旋和液晶中间相的情况。该研究的目的是从单链缺陷在材料层次结构中向上传播到由胶原蛋白形成的固态原纤维组装体的角度，深入了解胶原蛋白突变。体外进行的研究证明了这种方法在建立体外疾病模型方面的价值，因为胶原蛋白破坏程度可以通过点突变来重现，以显示对宏观特征的重大影响。傅里叶变换红外光谱、圆二色性、原子力显微镜和椭圆偏振光谱法用于评估组装后不同长度尺度上的结构和形态变化。结果表明，胶原蛋白肽中甘氨酸到丙氨酸再到天冬氨酸的单取代逐渐破坏正常组装，表现为热稳定性降低、三螺旋结构丧失和中间相形成丧失。这种方法可以为研究用于控制羟基磷灰石形成的胶原蛋白生物材料模板以及与骨重塑相关的细胞信号变化（与疾病严重程度相关）提供基础。
