Science2014-06-10 3:27 PM

首个重鼠建立从原子水平揭示组织的发育情况 NMR Spectroscopy of Native and in Vitro Tissues Implicates PolyADP Ribose in Biomineralization

论文摘要 

研究人员如何知道他们在实验室中所生长的组织,例如像骨这样的组织,与作为一种精确模型的生物学组织有足够的相似性呢?到目前为止,还没有一种方法能在原子水平对这种体外模型中的复杂材料,如细胞外基质,与真实组织的结构相比较。

但Wing Ying Chow及其同事证实核磁共振(NMR)光谱可被用来做到这一点——他们用活的小鼠组织来指导体外骨模型发育的研发。研究人员设计了一种富含碳-13和氮-15同位素的体重较重的小鼠;这两种同位素皆可轻易地被NMR所检测并能增进胶原组织的分辨率。他们用该小鼠的NMR光谱作为某种“指纹”来与某种他们正在研究的骨发育模型进行比较。详细的观察揭示了重鼠组织与它们的体外模型之间的细微差异,而研究人员接着利用该差异在实验室中制作了更像原生状的组织。

出人意料的是,Chow和其他的研究人员发现,一种叫做PAR的分子也会与发育中骨组织的胶原基质矿物质结合;PAR在通常情况下是与核蛋白相关的。他们说,他们在原子尺度探测组织的新方法可能会在组织工程或药物输送中找到应用。

Abstract 

Nuclear magnetic resonance (NMR) spectroscopy is useful to determine molecular structure in tissues grown in vitro only if their fidelity, relative to native tissue, can be established. Here, we use multidimensional NMR spectra of animal and in vitro model tissues as fingerprints of their respective molecular structures, allowing us to compare the intact tissues at atomic length scales. To obtain spectra from animal tissues, we developed a heavy mouse enriched by about 20% in the NMR-active isotopes carbon-13 and nitrogen-15. The resulting spectra allowed us to refine an in vitro model of developing bone and to probe its detailed structure. The identification of an unexpected molecule, poly(adenosine diphosphate ribose), that may be implicated in calcification of the bone matrix, illustrates the analytical power of this approach.

Fundamentals of Bone Formation

In vitro models can help guide research for tissue engineering or drug delivery, but the extent to which results from in vitro experiments may mimic in vivo ones will depend on the robustness of the model. For complex tissues like the extracellular matrix or bone, this means matching the chemical organization of the tissue at both the atomic scale and the structural level. Chow et al. (p. 742) used nuclear magnetic resonance (NMR) spectroscopy to analyze a sample on both these length scales. First an isotope-enriched mouse was produced to enhance the NMR signal. Samples from these mice were then used to study the extracellular matrix of developing bone and the calcification front during fetal bone growth.

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