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Simulating Cortical

Actin Networks
Group Meeting 25th February 2020
What simplifications are made in
AFINES?
AFINES Simulation
• Agent-based
• Molecular Dynamics Simulation
• Coarse-grained
• Quasi-2D (No Volume Exclusion on a 2D plane, OK as below packing
concentration)
• Object Oriented Program in C++
• Periodic, Lees-Edwards or Reflective Boundary Conditions
Limitations of the model
• The greatest force present in the simulation must be inversely
proportional to the timestep
• Therefore, we are limited to:
• Long crosslinkers, filamin lengths (100nm approx.)
• Flexible Crosslinkers and Myosin Motors
• Lower concentrations
• And or lower Duty ratios
Modelling Dynamics and Boundary
Conditions
•  Langevin Dynamics
• Low (kinematic) viscosity (10-6m2 s-1)
• Low Reynold’s Number (10-4)
• Overdamped Limit
• Stokes’ Drag
Modelling Binding Kinetics
• Load-dependent binding and unbinding
• Cutoff distance
Modelling Actin Filaments
• WLC behaviour
• Beads linked with linear springs
• Torsional spring limits bending
• Bending modulus much smaller than stretching stiffness
• Flexible but relatively inextensible
Modelling Cross-linkers
• Bind to a pair of filaments and act as a linear spring
• High stiffness but modelled at filament links stiffness to reduce
computational cost
• Binding kinetics depend upon the load
• Force is distributed over the attached filaments
Modelling Myosin Motors
• Can be thought of as an active cross-linker
• Load dependent walk velocity along filament
• Exhibits sliding and buckling
• Reduced stall force to limit speed
• Maintains reasonable length
• Unbind rate higher at the barbed end
Statistical Fluctuation
Statistical Fluctuation
Persistence Length
Shear Stress
• Lees-Edwards Boundary Conditions
• Shear stiffening relationship depends on stiffness of cross-linker
• Stiff cross-linkers: differential elastic modulus due to filaments
• Compliant cross-linkers: Softer response
Contractil
e
Networks
Quantitative Measures
• Radial Distribution Function
• Divergence of the velocity field
• Mesh Size
Contractility
Three Network Structures
• Bundled
• Contracted
• Polarity Sorted
Quantitative Measures
• Barbed end radial
distribution
• Secondary peak for
polarity sorted network
• Contracted barbed ends
aggregate somewhat
• Contracted velocity
divergence more negative
than for bundling or
polarity-sorted
Stress Relaxation Curves

  𝑈 𝑡𝑜𝑡  

𝑡
𝜎= 𝜎 ( 𝑡 )= 𝐴 𝑡
−𝛼
𝑒 𝜏
+𝐵
𝜀𝑉
How does the Duty Ratio effect
Stress Relaxation?

τ = 0.61s τ = 1.10s τ = 1.87s


How does the Filament Length effect
Stress Relaxation?

τ = 1.10s τ = 4.31s
Possible routes to go down…
• Bimodal Length Distribution (Fritzsche Distribution of F-actin lengths)
• Branched networks
• Growing Filaments (F-actin depolymerisation)
• Implement Filament Turnover
• Include Volume Exclusion
• Non-Hookean Spring Potential (FENE Potential)

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