Quantifying the relation between bond number and myoblast proliferation
Quantifying the relation between bond number and myoblast proliferation
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DOI：
10.1039/b719928g
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发表时间：
2008-01-01
影响因子：
3.4
通讯作者：
Mooney, David J.
中科院分区：
文献类型：
--
作者：
Boontheekul, Tanyarut;Kong, Hyun-Joon;Mooney, David J.
细胞外基质的许多功能可以被整个分子的小肽片段(如精氨酸-甘氨酸-天冬氨酸(RGD)序列)所模拟，但这些肽的呈现对于它们对细胞的影响是至关重要的。生物材料提供的多肽可能只与细胞受体和黏附配体之间形成的键的数量有关，但缺乏量化键数量的工具限制了对这一假设的直接研究。在这项研究中，首先考察了不同的配体呈现形式(密度、亲和力和纳米级分布)对C2C12和人原代成肌细胞增殖的影响。增加配基密度或结合亲和力可促进C2C12细胞和人原代成肌细胞的增殖。簇状RGD配体的纳米级分布也影响C2C12细胞和人类原代成肌细胞的增殖，但以相反的方式。然后利用流变学技术和FRET技术来量化受体-配体相互作用的数量作为多肽呈现的函数。用这两种技术测得的RGD密度和亲和力越高，形成的键数越多，且键数与细胞生长速度相关。然而，纳米级多肽分布的影响似乎并不仅仅是键数的函数。总之，这些发现为肽递呈在调节细胞增殖中的作用提供了重要的洞察力，这项工作中开发的方法可能在探索黏附如何调节各种其他细胞功能和帮助开发细胞交互材料的设计标准方面具有重要的实用价值。
Many functions of the extracellular matrix can be mimicked by small peptide fragments (e. g., arginine-glycine-aspartic acid (RGD) sequence) of the entire molecule, but the presentation of the peptides is critical to their effects on cells. It is likely that some effects of peptide presentation from biomaterials simply relate to the number of bonds formed between cell receptors and the adhesion ligands, but a lack of tools to quantify bond number limits direct investigation of this assumption. The impact of different ligand presentations (density, affinity, and nanoscale distribution) on the proliferation of C2C12 and human primary myoblasts was first examined in this study. Increasing the ligand density or binding affinity led to a similar enhancement in proliferation of C2C12 cells and human primary myoblasts. The nanoscale distribution of clustered RGD ligands also influenced C2C12 cells and human primary myoblast proliferation, but in an opposing manner. A rheological technique and a FRET technique were then utilized to quantify the number of receptor-ligand interactions as a function of peptide presentation. Higher numbers of bonds were formed when the RGD density and affinity were increased, as measured with both techniques, and bond number correlated with cell growth rates. However, the influence of the nanoscale peptide distribution did not appear to be solely a function of bond number. Altogether, these findings provide significant insight to the role of peptide presentation in the regulation of cell proliferation, and the approaches developed in this work may have significant utility in probing how adhesion regulates a variety of other cellular functions and aid in developing design criterion for cell-interactive materials.