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.
Highlights
IntroductionIn addition to label-free live cell image analysis with reflection interference contrast microscopy (RICM)[21], we employed a novel assay utilizing intensive pressure waves induced by laser pulses (Fig. 1b) to quantify the adhesion strength of hematopoietic stem cells (HSC) to the in vitro model niche[22]
Correspondence and requests for materials should be addressed to Quantifying Adhesion Mechanisms and Dynamics of Human Hematopoietic Stem and Progenitor Cells
We have demonstrated that the binding of hematopoietic stem cells (HSC) to the niche model is a cooperative process, and the adhesion mediated by the CXCR4- stromal cell-derived factor 1a (SDF1a) axis is stronger than that by homophilic N-cadherin binding
Summary
In addition to label-free live cell image analysis with reflection interference contrast microscopy (RICM)[21], we employed a novel assay utilizing intensive pressure waves induced by laser pulses (Fig. 1b) to quantify the adhesion strength of HSC to the in vitro model niche[22]. This technique utilizes a "shock wave" (a pressure wave traveling at a speed beyond the sound velocity) that is induced by a picosecond (ps) laser pulse focused near the substrate surface. The use of statistical physics methods has enabled us to identify different modes of shape deformation and motion of HSC as well as to assess the energy dissipation by HSC in the presence and absence of SDF1a, which is usually hidden behind stochastic noises
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