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Sci Rep. 2015 Mar 31;5:9370. doi: 10.1038/srep09370.

Quantifying adhesion mechanisms and dynamics of human hematopoietic stem and progenitor cells.

Author information

1
1] Physical Chemistry of Biosystems, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany [2] Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, 76021 Karlsruhe, Germany.
2
Physical Chemistry of Biosystems, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany.
3
1] Physical Chemistry of Biosystems, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany [2] Department of Chemistry, Faculty of Science, Saitama University, Saitama, 338-8570, Japan.
4
Department of Medicine V (Hematology, Oncology &Rheumatology), University of Heidelberg, 69120 Heidelberg, Germany.
5
1] Physical Chemistry of Biosystems, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany [2] Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, 76021 Karlsruhe, Germany [3] Institute for Integrated Cell-Material Sciences (WPI iCeMS), Kyoto University, 606-8501, Kyoto, Japan.

Abstract

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.

PMID:
25824493
PMCID:
PMC5380331
DOI:
10.1038/srep09370
[Indexed for MEDLINE]
Free PMC Article

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