VI: Modelling S.C. Migration

Created by Gabrielle Steppic

migration steps
1. protrusion at the frontal edge 2. focal adhesions at the frontal edge 3. contraction at the rear edge 4. focal adhesions at the rear edge

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TermDefinition
migration steps1. protrusion at the frontal edge 2. focal adhesions at the frontal edge 3. contraction at the rear edge 4. focal adhesions at the rear edge
active strains- decomposition of the deformation gradient - intensity of the strain - cyclic manner - chemotaxis - pulsatile movement
active strains = protrusions
decomposition of the deformation gradient is measured byF = Fse * Fsa
intensity of the strain is measured by Fsa = e0
cyclic manner is measured by Fsa = e0sin(2π * t/T)
chemotaxis is measured by Fsa= e0sin(2π * t/T) * i(θ)*i(θ) iθ = cosθ(t)ix+sinθ (t)iy
∂|Fsa|/∂t > 0protrusion
∂|Fsa|/∂t < 0contraction
frontal and rear edge adhesion forces are measured by regularized Heaviside functions
generalized Maxwell modelFsa = polymerization/depoly. Os/Fse = actin filaments Ofe, Ffe = organelles Ofv, Ffv = cytosol
output of maxwell modelO = Os + Of F = Fs + Ff
numerics generalized maxwell model2 eqns ρa = Divx(JσF^-T) θ̇ + θ − θinfinity/τinfinity
obstacles- regularized heaviside function - additional adhesion forces
2 strategies to avoid obstacles- velocity sensor / "run-and-tumble" - distance sensor / "look-and-run"
velocity sensor equationVc = 1/|Ωc|[differential]Ωc vdV
filtering the velocity helps to avoid oscillations d^2Vcf/dt^2 + 2fωf * dVcf/dt + ωfVcf = Vc
in the "run-and-tumble" model- if there is no obstacle: cell migrates towards θinfinity - if there is an obstacle: some rendition of regularized heaviside functions
pseudopods- membrane protrusions - perpendicular to the membrane
splitting of existing pseudopodszig-zag trajectory
new pseudopods at not active regionsany direction
measuring the active strain within migration with pseudopods- sum of the strain in each pseudopod - gradient along the pseudopod axis - uniform inside the pseudopod - gradient + uniform
static pseudopods
temporal sensing model- protrusion - multiple simultaneous pseudopods - minimal distance between pseudopods (5 degrees) - contraction - pseudopod best oriented towards the source - same frame as the source
spatial sensing model- protrusion; only one pseudopod at the time
durotaxis and polarityisotropy-anisotropy of the cell
durotaxis - functions to analyze substratesfunctions for stiff, soft, and viscous forces stiff: x < x0 soft: x > x0
eqns to analyze equilibrium and constitutive law of the cell
durotaxis - analyzing the solid phase of a cellσse=1/Jse * FseSseF^Tse anisotropic hyperelastic saint-venant material
durotaxis - anisotropic hyperelastic saint-venant materialSse = RCloc(R^TEseR)R^T R: found via rotation matrix; ploc = Rp Cloc: found via local elastic tensor Ese: found via green-lagrange tensor
durotaxis - in the local elastic tensor A and B come from their own fcns...soft substrate: E0 = Ea stiff substrate: Ea = 0.1E0
durotaxis - green-lagrange tensor - fluid phasediff eqns
durotaxis - adhesion forcesfunctions i can't make sense of
active strain of cell in durotaxis- radial protrusion and contraction - lamellipodium in the direction of migration d
durotaxis - soft vs. stiff substratethere is a difference that can only be seen in images that i can't put here. slides 58-61
durotaxis (discrete approach)- cellular potts model - boltzmann probability function to validate the trial spin - hamiltonian function - net energy difference
cellular potts model- 3D regular lattice -> center (x) and label σ(x) - subdomains with same label form discrete objects: medium, cell, substrate - iterative and stochastic reduction of energy - monte carlo-boltzmann dynamics
iterative and stochastic reduction of energyhamiltonian function (H)
monte carlo-boltzmann dynamicsbehavior of biological individuals
each timestep with in cellular potss model- randomly chosen lattice site (xsource) - allocation of its spin σ(xsource) to one neighbours xtarget randomly selected
durotaxisdoes not make sense to me