Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does...
Transcript of Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does...
![Page 1: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/1.jpg)
Andrea J. Liu Department of Physics & Astronomy
University of Pennsylvania
Cell Motility and Migration
Kun-Chun Lee Biophysics, UC DavisEdward Banigan Physics, UPennGareth Alexander Physics, UPennZemer Gitai Biology, PrincetonNed Wingreen Biology, PrincetonTajie Harris Pathobiology, UPennChris Hunter Pathobiology, UPenn
![Page 2: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/2.jpg)
Self-Assembly-Driven Motility
Neutrophil chasing Staphylococcus aurea
David Rogers, Vanderbilt Univ, 1959http://www.chem.uic.edu/fenteany/research/cell_migration/neutrophil.html
Courtesy of T. M. Svitkina, G.G. Borisy
Xenopus keratocytes
How does self-assembly of actin into branched networks lead to motion?
Kun-Chun Lee, Ed Banigan
![Page 3: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/3.jpg)
Disassembly-Driven Motility
Courtesy of C. W. Shebelut, J. M. Guberman, Z. Gitai
Caulobacter crescentus
How does the chromosome move across the cell during chromosomal segregation in certain asymmetric bacteria? Ed Banigan, Zemer Gitai, Ned Wingreen
![Page 4: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/4.jpg)
Actin Polymerization and Depolymerization
•A 3µm long filament turns over in 1 min in vivo•ATP hydrolysis provides polarity to filament growth
G-actinF-actin
Molecular Cell Biology, Lodish et al
Chen, Bernstein, Bamberg, Trends Biochem. Sci, 25, 19 (2000).
![Page 5: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/5.jpg)
Life cycle of Listeria monocytogenes
Uses actin polymerization to move!Same physics as cell crawling
Actin and Listeria Motility
CDC
![Page 6: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/6.jpg)
Without proteins that generate comet tail, Listeria can
How Listeria Spreads from Cell to Cell
Courtesy of Julie Theriot, http://cmgm.stanford.edu/theriot/
Speeded up x900 Speeded up x150
![Page 7: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/7.jpg)
How are growing ends localized behind Listeria?
Courtesy of J. Theriot, http://cmgm.stanford.edu/theriot/
x60
L. A. Cameron, T. M. Svitkina, D. Vignjevic, J. A. Theriot, G. G. Borisy, Current Biology, 11, 130 (2001).
• Arp2/3 complex binds to F-actin to nucleate new branches
• Arp2/3 is activated at back end of Listeria
T. M. Svitkina, G. G. Borisy, J. Cell Biol. 145, 1009 (1999).
How does far-from-equilibrium self-assembly into a branched structure lead to motility?
![Page 8: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/8.jpg)
Brownian Dynamics Simulations
• Polymerization at + end (k+)
• Depolymerization at - end (k-)
• Branching (ka)
• Debranching (kd)
• CappingK. C. Lee and A. J. Liu, Biophys. J. 95, 4529 (2008).
![Page 9: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/9.jpg)
We See Motility!
2D projection of 3D simulationMotion allowed in ±z direction, only
K. C. Lee and A. J. Liu, Biophys. J. 95, 4529 (2008).
![Page 10: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/10.jpg)
Center of drag is stationaryCenter of mass can move
Newton’s Third Law
Ftail = −
Fdisk
ς tailvtail = −ςdisk
vdisk
vdisk = −ς tailςdisk
vtail
>1
![Page 11: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/11.jpg)
• Stiff/flexible: 60+%/5% of force from tips
• At low viscosity, speed is independent of filament stiffness!
• Mechanism cannot depend on whether force comes from tips
Problem with Accepted Mechanism
A. Mogilner and G. Oster, Biophys J., 84, 1591 (2003).
Courtesy of S. Kuo
![Page 12: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/12.jpg)
• Disk activates Arp2/3, which recruits F-actin
• Concentration of F-actin high behind the disk compared to average
• If disk repels actin, then disk will move forwards to avoid F-actin
• In real system, concentration gradient is
Origin of Motility
disk
K. C. Lee and A. J. Liu, Biophys. J. 95, 4529 (2008).
Courtesy of J. Theriot
![Page 13: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/13.jpg)
But Filaments are Bound to Disk
• Some sites on disk have attraction ε to filament tips
V (r,ψ ) = ε σ 14
r14−σ 12
r12
cos4ψ
E. Banigan
Specific binding of filaments to the disk
does not destroy motility
H. Boukellal, O. Campas, J.-F. Joanny, J. Prost, C. Sykes, PRE 69, 061906 (’04).
![Page 14: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/14.jpg)
New Proposed Mechanism for Actin Motility
Why do bagpipe players always walk while they play?
To get away from the noise.
K. C. Lee and A. J. Liu, Biophys. J. 95, 4529 (2008), Biophys. J. 97, 1295 (2009).
![Page 15: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/15.jpg)
Chromosomal Segregation in Caulobacter
Courtesy of C. W. Shebelut, J. M. Guberman, Z. Gitai
Caulobacter crescentus
![Page 16: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/16.jpg)
Asymmetric Cell Division
• Most cells divide symmetrically
• What is the mechanism for chromosomal motility?
swarmer
cell
stalked
cell
Caulobacter crescentus and Vibrio cholerae divide asymmetrically
![Page 17: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/17.jpg)
Chromosomal Segregation in C. crescentus and V.
Courtesy of C. W. Shebelut, J. M. Guberman, Z. Gitai
Caulobacter crescentus
We are interested in 4th stage
How does the chromosome (ori) scoot across the cell?
![Page 18: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/18.jpg)
A Closer Look at Process
replicationParB on origin attaches to ParA
ParA disassembles and ori moves
origin and terminus switch places
terminusorigin 1origin 2 origin 1
ori2/ParB ParA
• Origin is decorated with ParB which binds to and hydrolyzes ParA• ParA filament structure depolymerizes and drags ParB along
![Page 19: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/19.jpg)
We See Translocation
![Page 20: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/20.jpg)
Concentration Gradient Drives Motion
• System uses depolymerization to create steady-state
![Page 21: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/21.jpg)
PARTICLE MOTION IN A CONCENTRATION GRADIENTDiffusiophoresis
• Actin-polymerization-driven motility arises from repulsions between “particle” (Listeria bacterium) and A (actin)
• ParA/ParB-driven-chromosomal segregation arises from attraction between “particle” (ParB) and A (ParA)
![Page 22: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/22.jpg)
Self-Diffusiophoresis
• But there is no externally-imposed gradient of actin or ParA!
• In Listeria, bacterium activates actin polymerization to create its own actin concentration gradient
• In ParA case, ParB-decorated chromosome in Caulobacter uses ParA depolymerization to create its own ParA gradient
![Page 23: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/23.jpg)
Self-Diffusiophoresis is Very GeneralGolestanian, Liverpool, Ajdari, PRL 94, 220801 (2005).
• Coat Janus colloids with Pt and put in H2O2 solution
•
H2O2 → H2O +12O2
Deff = D +14V 2τ R
Diffusion enhanced by propulsion
velocity V
Howse, et al. PRL 99,
048102 (2007).
![Page 24: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/24.jpg)
PARTICLE MOTION IN A CONCENTRATION GRADIENTSelf-diffusiophoresis occurs in a fluid
Motion involves a balance between diffusion and advection
G. Alexander
![Page 25: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/25.jpg)
COMPARISONSelf-diffusiophoresis at high and low Peclet number
![Page 26: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/26.jpg)
Summary
• Physical mechanism underlying actin-polymerization-driven motility and chromosomal translocation in Caulobacter is self-diffusiophoresis
• But since branched actin network and ParA bundle do not diffuse; this is a new regime of self-diffusiophoresis, dominated by advection, not diffusion
• This affects the resulting motion profoundly• Only two steady-state scenarios
– repulsive producer (actin-driven motility)– attractive consumer (ParAB-driven motility)
![Page 27: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/27.jpg)
Cell Migration
How do white blood cells migrate in response to infection?
Neutrophil chasing Staphylococcus aurea
David Rogers, Vanderbilt Univ, 1959http://www.chem.uic.edu/fenteany/research/cell_migration/neutrophil.html
CD8+ T cells hunting Toxoplasma gondii
Tajie Harris, David Christian, Chris Hunter
![Page 28: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/28.jpg)
T cells in brain
• T cells enter brain in response to infection
• CD8+ T cells hunt down and kill Toxoplasma gondii
• What are their migration statistics?
T cell
Astrocyte
Chemokines
Blood
Blood-brain barrier
Brain
T. gondii
![Page 29: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/29.jpg)
Mean-squared Displacement
• For ordinary Brownian random walks, mean-squared displacement is diffusive
• For T cells (control), mean-squared displacement is superdiffusive1 10
T im e, t (m in )
1
10
100
MS
D (µ
m )
C on tro lC hem okine-neutra lized
2
1
(anti-C X C L10-trea ted)
![Page 30: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/30.jpg)
Correlations are long-lived
• Correlations of displacements r during time interval t, separated by time τ
• For Brownian walkers, correlations decay exponentially
• For T cells, correlations decay
K(t, !) =!r(0, t) · r(!, ! + t)"
!r2(0, 0)"
1 10T im e, τ (m in )
0 .01
0.1
1
Cor
rela
tion
func
tion,
K(τ
, t)
C on tro lE xponentia l fit
![Page 31: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/31.jpg)
Displacement Distribution
• For Brownian walkers, displacement distribution is always Gaussian with scale factor ς that increases with time1/2
• T cell distributions show scaling collapse– But not onto a
Gaussian– ς~t0.63
10-2 10-1 100 101 102
D isp lacem ent, r(t) (µm )10-4
10-3
10-2
10-1
100
Pro
babi
lity
dens
ity, P
(r(t
))
t = 0 .37m int = 1 .1m int = 2 .9m int = 4 .8m int = 9 .9m in
ς(t)
ς(t)*
10-1 100 101
S ca led d isp lacem ent, ρ
10-4
10-3
10-2
10-1
100
Sca
led
prob
abili
ty, P
(ρ)
G auss ian
1 10T im e, t (m in )
0 .1
1
10
Sca
le fa
ctor
, ζ(t
) (µ
m) C on tro l
0 .63
![Page 32: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/32.jpg)
• Lévy walks have steps drawn from power-law distribution
• Such walks– are superdiffusive– have long-time correlations– exhibit scaling collapse of displacement distributions– Scaling distribution is wider than Gaussian
• Used by marine predators (Humphries, et al. Nature, 465, 1066 (2010).
Lévy walks
Pµ(x) ! x!µ
blue shark
yellowfin tuna
![Page 33: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/33.jpg)
T cells execute generalized Lévy walks
10-2 10-1 100 101 102
D isp lacem ent, r(t) (µm )10-4
10-3
10-2
10-1
100
Pro
babi
lity
dens
ity, P
(r(t
))
t = 0 .37m int = 1 .1m int = 2 .9m int = 4 .8m int = 9 .9m in
C ontro l
1 10T im e, τ (m in )
0 .01
0.1
1
Cor
rela
tion
func
tion,
K(τ
, t)
C on tro lM ode l
1 10T im e, t (m in )
1
10
100
MS
D (µ
m )
C on tro l
2 1
![Page 34: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/34.jpg)
Generalized Lévy walks
• Our model: cells run a Lévy-distributed distance (µrun=2.15) and then pause a Lévy-distributed time (µpause=1.7)
![Page 35: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/35.jpg)
Search and Capture
• Generalized Lévy searches are more efficient than Brownian searches
T cellsParasiteTrajectory
η = targets foundtotal distance traveled
0 50 100 150 200Targe t rad ius, a (µm )
10-9
10-8
10-7
10-6
10-5
10-4
Cap
ture
effi
cien
cy, η
(µ
m )
G enera lized Levy searchD iffus ive search
-1
![Page 36: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/36.jpg)
Final Remarks
• Self-diffusiophoresis is the simplest form of chemotaxis– Maybe it isn’t surprising that it is exploited in cells
• CD8+ T cells hunt T. gondii much as predators hunt prey– Is this due to factors internal or external to the cell?– Do other cells of our immune system have migration
statistics adapted to their function?
• Physicists tend to think mostly about systems in equilibrium– Most many-body phenomena in the world occur far from
equilibrium– Simple, undiscovered, far-from-equilibrium phenomena still
![Page 37: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/37.jpg)
Thanks to
Ed Banigan
Kun-Chun Lee
Gareth Alexander
Tajie Harris
Zemer Gitai
Ned Wingreen
Chris Hunter
NSF-DMR-1104637
![Page 38: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/38.jpg)
Curie Model
F. Gerbal, P. Chaikin, Y. Rabin and J. Prost, Biophys. J. 79, 2259 (2000)
• Main ingredient is competition between compressive (forwards) stresses and tensile (backwards) stresses
• Compressive stresses put in by hand• Actin comet tail is assumed to be elastic medium• F-v relation from dep. of polymerization rate on stress• BUT
– Motility is observed even in absence of crosslinkers
![Page 39: Cell Motility and Migration - Astronomy · J. M. Guberman, Z. Gitai Caulobacter crescentus How does the chromosome move across the cell during chromosomal segregation in certain asymmetric](https://reader036.fdocuments.in/reader036/viewer/2022071212/6023edad4172970a7e2cb793/html5/thumbnails/39.jpg)
Comparison with Previous Simulations
e.g. Alberts & Odell, PLOS Biology, 2, 2054 (2004).
• Realistic rates
• Realistic numbers of filaments
• BUT– Monomers only exist when they
are in filaments; artificial mass transfer gives rise to motility as an artifact
– Artificial forces used to avoid
Our work• Physically-consistent model• Don’t violate important physical
principles• BUT
– Depolymerization rate is too high
– [G-actin] is too high– Filament stiffness is too low