Dimensional Control of Cancer Cell Migration

Department of Chemical and Biomolecular Engineering, and Johns Hopkins Physical Sciences-Oncology Center, The Johns Hopkins University, Baltimore, Maryland. Electronic address: .
Biophysical Journal (Impact Factor: 3.97). 01/2013; 104(2):279-80. DOI: 10.1016/j.bpj.2012.12.016
Source: PubMed
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    • "The cross-sectional areas (Wolf et al., 2009) of pores/channels encountered in vivo range from 10 to >300 mm 2 , suggesting that cells migrating in vivo experience varying degrees of physical confinement. Mounting evidence suggests that physical confinement alters cell migration mechanisms (Balzer et al., 2012; Konstantopoulos et al., 2013; Pathak and Kumar, 2012; Stroka et al., 2013). "
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    ABSTRACT: Cell migration is a critical process for diverse (patho)physiological phenomena. Intriguingly, cell migration through physically confined spaces can persist even when typical hallmarks of 2D planar migration, such as actin polymerization and myosin II-mediated contractility, are inhibited. Here, we present an integrated experimental and theoretical approach ("Osmotic Engine Model") and demonstrate that directed water permeation is a major mechanism of cell migration in confined microenvironments. Using microfluidic and imaging techniques along with mathematical modeling, we show that tumor cells confined in a narrow channel establish a polarized distribution of Na(+)/H(+) pumps and aquaporins in the cell membrane, which creates a net inflow of water and ions at the cell leading edge and a net outflow of water and ions at the trailing edge, leading to net cell displacement. Collectively, this study presents an alternate mechanism of cell migration in confinement that depends on cell-volume regulation via water permeation.
    Cell 04/2014; 157(3). DOI:10.1016/j.cell.2014.02.052 · 32.24 Impact Factor
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    ABSTRACT: Suitable asymmetric microstructures can be used to control the direction of motion in microorganism populations. This rectification process makes it possible to accumulate swimmers in a region of space or to sort different swimmers. Here we study numerically how the separation process depends on the specific motility strategies of the microorganisms involved. Crucial properties such as the separation efficiency and the separation time for two bacterial strains are precisely defined and evaluated. In particular, the sorting of two bacterial populations inoculated in a box consisting of a series of chambers separated by columns of asymmetric obstacles is investigated. We show how the sorting efficiency is enhanced by these obstacles and conclude that this kind of sorting can be efficiently used even when the involved populations differ only in one aspect of their swimming strategy.
    Central European Journal of Physics 05/2013; 11(12). DOI:10.2478/s11534-013-0300-7 · 1.09 Impact Factor
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    ABSTRACT: Mechanical interaction between the cell and its extracellular matrix (ECM) regulates cellular behaviors, including proliferation, differentiation, adhesion, and migration. Cells require the three dimensional (3D) architectural support of the ECM to perform physiologically realistic functions. However, current understanding of cell-ECM and cell-cell mechanical interactions is largely derived from 2D cell traction force microscopy, in which cells are cultured on a flat substrate. 3D cell traction microscopy is emerging for mapping traction fields of single animal cells embedded in either synthetic or natively derived fibrous gels. We discuss here the development of 3D cell traction microscopy, its current limitations, and perspectives on the future of this technology. Emphasis is placed on strategies for applying 3D cell traction microscopy to individual tumor cells migration within collagen gels.
    Experimental Cell Research 06/2013; 319(16). DOI:10.1016/j.yexcr.2013.06.009 · 3.25 Impact Factor
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