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Explaining the dynamic steady state of actin networks
in silico
in vitro
ADF/Cofilin
Explaining the dynamic steady state of actin networks
CytomorphoLab, Grenoble
in vitro
Laurent Blanchoin
Tea Aleksandra Icheva
Courant Institute, New York University
Angelika Manhart
from [Pollard et al, 2003]
Alex Mogilner
in silico
Width
University College London
June 2021, SMB
Length
Laurent Blanchoin
Manuel Thery
Tea Aleksandra Icheva
Christophe Guerin
Tobbias Klar
Rajaa Boujemaa-Paterski
Alex Mogilner
Funding
1. How can we mathematically capture the macroscopic fragmentation?
2. What determines equilibrium network length?
3. How does cofilin affect turning mechanisms?
H2020 European Research Council, Agence Nationale de la Recherche, Universite Greoble Alpes, Army Research Office
Explains how dynamic steady state of actin emerges from biochemical and structural feedbacks
How does cofilin (un)bind?
Predictions I: Varying Actin Density and Cofilin Background
Cofilin binding dynamics
A reaction-advection-diffusion model for cofilin
Ingredient 1: Estimating bound cofilin for given network length
Bound cofilin:
network speed
unbinding
binding
Network fragmentation
free cofilin
Free cofilin:
actin
diffusion
added cofilin
Bound cofilin
Free cofilin
V
Results & Findings III
Results & Findings I
network length
network width
Cofilin affects network elasticity affects steering
Network equilibrium length determined by balance of: Cofilin binding dynamics and network fragmentation
Network fragmentation
How does the network fall apart?
Predictions II: Varying Network Width
Cofilin binding dynamics
Wider networks grow longer, because of depletion
Network fragmentation
Correctly predicts network equilibrium length if we
Ingredient 2: Estimating the network length from bound cofilin
Stochastic, discrete actin network fragmentation model
- vary amount of cofilin added C0
- vary network width W
- vary actin density A
Data shows macroscopic fragmentation!
Boujemaa-Paterski et. al. 2017
Cofilin binding dynamics
Key function for model behavior:
Analytical Approximation
Local breakage rate per node
Use experimental data to find best exponents
Bound cofilin
Actin
A.M. et al, Quantitative regulation of the dynamic steady state of actin networks. eLife (2019)
angelikamanhart.github.io
nuclear count
relative y-position