Abstract
We studied the dynamic behavior of human hematopoietic stem cells (HSC) on the in vitro model of bone marrow surfaces in the absence and presence of chemokine (SDF1α). The deformation and migration of cells were investigated by varying the chemokine concentration and surface density of ligand molecules. Since HSC used in this study were primary cells extracted from the human umbilical cord blood, it is not possible to introduce molecular reporter systems before or during the live cell imaging. To account for the experimental observations, we propose a simple and general theoretical model for cell crawling. In contrast to other theoretical models reported previously, our model focuses on the nonlinear coupling between shape deformation and translational motion and is free from any molecular-level process. Therefore, it is ideally suited for the comparison with our experimental results. We have demonstrated that the results in the absence of SDF1α were well recapitulated by the linear model, while the nonlinear model is necessary to reproduce the elongated migration observed in the presence of SDF1α. The combination of the simple theoretical model and the label-free, live cell observations of human primary cells opens a large potential to numerically identify the differential effects of extrinsic factors such as chemokines, growth factors, and clinical drugs on dynamic phenotypes of primary cells.
Highlights
We fabricated the surrogate niche model surface based on planar lipid membranes displaying precisely defined concentrations of ligand molecules SDF1α or N-cadherin11
The power spectrum analysis of stochastic morphological dynamics in Fourier space further unraveled that the energy dissipation of hematopoietic stem cells (HSC) by oscillatory deformation is strongly damped by the presence of physiological level of soluble SDF1α (5 ng/mL)
The superposed snapshots of a migrating human HSC and the trajectory are depicted in panels (c) and (d), respectively
Summary
We fabricated the surrogate niche model surface based on planar lipid membranes displaying precisely defined concentrations of ligand molecules SDF1α or N-cadherin. By sharply focusing on deformation and migration, which are accessible from the label-free, live cell images, our models can be quantitatively compared to the experimental results This enabled us to numerically represent the effect of chemokine SDF-1α as the nonlinear coupling in the equation of motion, which distinctly alters the persistence of migration trajectories. Such an interdisciplinary combination of dynamic phenotypes of cells and theoretical models opens new avenue to discriminate differential functions of clinical drugs compared to that of natural chemokine
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