Quantifying adhesion mechanisms and dynamics of human hematopoietic stem and progenitor cells.
Quantifying adhesion mechanisms and dynamics of human hematopoietic stem and progenitor cells.
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DOI：
10.1038/srep09370
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发表时间：
2015-03-31
影响因子：
4.6
通讯作者：
Ho AD
中科院分区：
文献类型：
--
作者：
Burk AS;Monzel C;Yoshikawa HY;Wuchter P;Saffrich R;Eckstein V;Tanaka M;Ho AD
使用平面脂膜与精确定义的浓度的特定配体，我们已经确定了人类造血干细胞（HSC）和骨髓龛之间的结合强度。通过（a）粘附细胞的分数，（B）紧密粘附的面积，和（c）细胞脱离的临界压力，量化通过SDF 1 α-CXCR 4或N-钙粘蛋白轴的HSC粘附到替代小生境模型的相对显著性。我们已经证明HSC与niche模型的结合是一个协同的过程，并且CXCR 4-SDF 1 α轴介导的粘附比同嗜性N-cadherin结合更强。随机形态动力学的统计图像分析揭示了HSC通过振荡变形耗散能量。结合体外生态位模型和新的物理工具，使我们能够定量确定正常造血干细胞与白血病母细胞之间的骨髓生态位的结合机制的相对意义。
Using planar lipid membranes with precisely defined concentrations of specific ligands, we have determined the binding strength between human hematopoietic stem cells (HSC) and the bone marrow niche. The relative significance of HSC adhesion to the surrogate niche models via SDF1α-CXCR4 or N-cadherin axes was quantified by (a) the fraction of adherent cells, (b) the area of tight adhesion, and (c) the critical pressure for cell detachment. We have demonstrated that the binding of HSC to the niche model is a cooperative process, and the adhesion mediated by the CXCR4- SDF1α axis is stronger than that by homophilic N-cadherin binding. The statistical image analysis of stochastic morphological dynamics unraveled that HSC dissipated energy by undergoing oscillatory deformation. The combination of an in vitro niche model and novel physical tools has enabled us to quantitatively determine the relative significance of binding mechanisms between normal HSC versus leukemia blasts to the bone marrow niche.