examples of confined migration
tumorogenesis
sub-cellular and sub-nuclear pores
tunnel-like trucks
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| Term | Definition |
|---|---|
| examples of confined migration | tumorogenesis sub-cellular and sub-nuclear pores tunnel-like trucks |
| tumorogenesis | from primary to secondary tumor metastatis development |
| sub-cellular and sub-nuclear pores | from 1 μm to 10 μm |
| tunnel-like trucks | 3 μm to 30 μm in width and from 100 μm to 600 μm in length |
| confined migration in tumors | exhibits aligned, bundled collagen fibers fibrillar collagen along or within blood vessels has epithelial or endothelial surfaces encased in muscle fibre |
| experimental approaches | - biomimetic hydrogels - micro-channels - grooved substrates - microcontact-printed and micro-patterned lines - vertical confinement devices - micropost arrays |
| biomimetic hydrogels | 3D gels formed of extracellular matrix proteins or chemically produced polymers |
| micro-channels devices | rectangular cross-sections with widths and heights between 3 μm and 50 μm |
| grooved substrates | substrates with parallel, rectangular or trapezoidal troughs that run unidirectionally for lengths much greater than the cell diameter |
| microcontact-printed and micro-patterned lines | thin stripes or patterns of a polymer are deposited on a 2D surface that is otherwise non-adhesive to cells |
| vertical confinement devices | - cells plated on a 2D substrate are sandwiched beneath a PDMS roof - free to migrate laterally but confined at their basal and apical surfaces |
| micropost arrays | defined but discontinuous barriers to cell migration in the form of vertical posts |
| nucleus role in confined migration | - most voluminous - stiffest - nucleoplasm (≅ 25 Pa) + lamina (≅ 3000 Pa) - critical treshold: 7 μm in collagen gels - modulation of stiffness - knockdown of lamin A |
| determinants of confined migration | confined cells high cellular adhesion high degree of cellular contractility linear elastic matrix fibroblasts present actin polymerization inhibited |
| nucleus mechanics | o mechanical stress and strain o localized ruptures of the lamina - DNA damage o apoptosis without repair |
| mechanicall model of confined migration has | o 2D geometry o cell modeled as a hybrid continuum - organelles represented by characteristic functions o deformation gradient decomposition o generalized Maxwell model o micro-channel with rigid walls |
| constitutive law of confined migration | o generalized Maxwell model o nucleus - nucleoplasm (fluid phase) - lamina (solid phase) o cytoplasm - cytosol (fluid phase) - membrane (solid phase) o polymerization and depolymerization in the cytosol |
| some mathematical equations that can be used to model confined migration | - global equilibrium - active strains - adhesion forces - micro-channels contact force |
| micropillared substrate | o quantify nuclear forces and self strain o is gravity driving nucleus movement ? o is the nucleus pushed or pulled ? -> contractile fibers - above the nucleus: perinuclear actin cap (PAC) - around the pillar beneath the nucleus |
| spreading of a micropillared substrate | o passive phase - cell settles under gravity action - deforms depending on its stiffness o active phase - protrusion and contraction |
| constitutive law of micropillared substrate is measured with | o generalized Maxwell model - solid and fluid phases - active strains in the cytosol |
| some forces that can be measured to mathematically model migration on a micropillared substrate are | gravity contact force adhesive-spreading force |
| active strains of confined migration | - two cellular regions results: nucleus displacement and inverted gravity has negligible effect |