By Tarun Meena Under the Guidance of Prof. Mandar M.

Inamdar Department of Civil Engineering, IIT Bombay

 Many aspects of cellular physiology rely on the ability

Introduction

to control mechanics across the cells

E.g. cells must able to maintain their shapes when

subjected to the external force

The varied mechanical behaviour of cell is determined

to a large degree by networks of filamentous protein called Cytoskeleton

 The objective of thesis is to understand the mechanics

Objective of the thesis

of filament network
We discuss the rheology of F-actin networks and

highlight how the small change in network composition can qualitatively change the mechanical response

 The cytoskeleton is cellular scaffolding or skeleton Function of cytoskeleton are

Cytoskeleton

Establishing cell shape Providing mechanical strength Locomotion and muscle fiber contraction Cell motility Chromosome separation Cell motility Ensure proper division of cell during cellular production

Existing Models
Elasticity of Stiff Polymer Networks This model is about the elasticity of a two dimensional network of rigid rod
The random network was generated by placing N line

Both positions and orientation are random distributed

objects of equal lengths l on a plane with area A L2

For understanding the elasticity two dimension model

is defined as below

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Figure: Typical networks at high and low densities. The distribution shown in false colors; the load on filament increases from blue to red. the left network has 99.99% of the strain energy stored in bending modes. In contrast, the right network has only 5% of the energy stored in bending; the remainder is stored in compression mode.

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According to the model, For high densities and thick

rods, where compressional stiffness is lower or comparable to the bending stiffness, the shear modulus scales linearly with the filament compressional modulus and the number of filament per unit area.

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Elasticity of Planar Network In this model the fiber axial deformation was considered This model account for microscopic deformation for the elastic stiffness of planar Filament Networks with all possible lengths and orientations. They suggested that the effective stiffness of a planar random Filament Network increases with the increase of Arial density Arial density, which can be measured by the number of fibers per unit area(fiber concentration)

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Figure :Deformation of typical fiber network under uniaxial tension

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The constitutive relation derived in this case for the effective stiffness of random Filament Network is as follows

Where,

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Passive and Active micro-rheology for crosslinked F-actin networks in vitro According to the model if the length of the filament is comparable to mesh size many loose end exist which contribute little to stiffness of the network
Reducing the filament length leas to more loose ends,

thereby altering network connectivity, as a result network is less capable of withstanding stress and therefore exhibit smaller modulus

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(A) (B) Figure : F-actin network organized by long(A) and short(B) actin filaments at identical concentration of actin filaments and cross linkers

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The network shown above, the network with long

They suggested that this difference in the structure

filaments(A) is regularly arranged while the network with short filament length(B) forms incomplete loops with many loose ends would cause the network with short filaments to be less stiff than the one with long filaments

 The Finite element analysis(FEA) method is a powerful

Modelling and analysis

technique for approximate solutions to a variety of real world engineering problems The basic idea of the finite element method is to break up a continuum into discrete number of small elements and expressing the unknown field variables in terms of the assumed approximating functions within each element FEM package such as ABAQUS enable to solve more complex element behaviour to be model

Assumption made in the Modelling of Filament Network

While modeling several assumptions have to made in order to simplify and practically model the actual system. The Key assumptions are as follows The fibers are straight and oriented in the same plane The fibers are randomly distributed The deformation is linearly elastic Beam cross section is assumed to be circular Effect of the medium, in which fiber networks is, being assumed negligible

Procedure used in modelling of the Filament Network in ABAQUS

For the filament network analysis, step by step procedure is as follows Sketched the two dimensional geometry of the filament network and created a part representing the network Defined the material properties and section properties of the network Assembled the model and created instance of the geometry Meshed the frame

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Applied the boundary conditions at the ends of the

filament network Created job named fil Network and submitted for analysis Observed the analysis result The above procedure was repeated each time for change in network composition separately

Random Network formulation

A two dimensional filament networks defined as as set

of independent short line segments on a two dimensional plane. In the network, at y=0;x=0 and x=L hinge and roller condition is applied Varying Displacement is provided at y=L i.e. at the top of the surface For the fixed value of displacement force has been calculated

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Figure : Model of the Network with vertical displacement and support condition

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The model is analysed using static linear analysis

procedure The reaction is obtained on the upper surface of the network and summed to the total reaction force in ydirection Elastic modulus of the network can be calculated as
RF2 Ec L disp. L

Result and discussion

Effective elasticity of the filament network The load-displacement curve is obtained for a network with Length of fiber 20m
Elasticity of the fibers is assumed to be
E=2x1011 N m2

for

the analysis

Reaction force at the surface is calculated for the

displacement in vertical direction

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(A) (B) Figure Model of the Network with vertical displacement and support condition (A) and its deformed shape (B)

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Fig: Reaction Force Vs Displacement of the filament Network
4,50E+10
4,00E+10 3,50E+10 Reaction Force(N)

3,00E+10
2,50E+10 2,00E+10

1,50E+10
1,00E+10 5,00E+09

0,00E+00
0 0,2 0,4 0,6 0,8 Displacement(m) 1 1,2 1,4 1,6

Figure: Plot of Reaction Force (N) Vs Displacement (m)

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The effective elasticity of the network. i.e. ratio of the elasticity of the network with the elasticity of the filament,

Ec =0.14 E

Effect of variation in density on the filament network

To study the effect of variation in elasticity two models

of different density is created

Applying BCs hinges and rollers at x=0,y=0 and x=50m
Keep the length of the fibers 20m for both of the

model and give displacement in the vertical direction

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(A) (B) Figure : Low density Network(A) and High density Network(B)

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(A) (B) Figure : Deformed shapes of the low Density network (A) and High Density Network (B)

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Reaction Force Vs Displacement
4,50E+10 4,00E+10 3,50E+10 Reaction Force(N) 3,00E+10 2,50E+10 2,00E+10 1,50E+10 Fig: Reaction Force Vs Displacement of low density Network Fig: Reaction Force Vs Displacement of High density Network

1,00E+10
5,00E+09 0,00E+00 0 0,5 Displacement(m) 1 1,5

Figure : Plot of Reaction Force Vs Displacement for low Density network (A) and High Density Network (B)

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2.822E+10 N m2

From the analysis, The elasticity of the network A(low

density network)comes out to be 3.00E+09 N2 while m elasticity of the network B(high density network) is

i.e. elasticity of the network increased with the

increase in density of the network The above result can also be verified with the similar model developed by X.-F. Wu, Y. A(6) where they suggested that the effective stiffness of a planar random Filament network increases with the increase of elasticity

 For the analysis, we created models of network with

Comparison of Network with long filaments and short filaments

short filaments and network with long filaments

Applying BCs hinges and rollers at x=0,y=0 and

x=100m
Analysis and comparison of both of the network is as

follows

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(A)

(B)

Figure : F-actin Network organized by long (A) and short (B) actin filaments at identical concentration of filaments and intersections

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(A) (B) Figure : Deformed shape of F-actin Network organized by long (A) and short (B) actin filaments at identical concentration of filaments and intersections

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Reaction force Vs Displacement
5,00E+10 4,50E+10

4,00E+10
3,50E+10 Reaction force(N) 3,00E+10 2,50E+10 2,00E+10 1,50E+10 1,00E+10 5,00E+09 0,00E+00 Fig: Reaction Force Vs Displacement of Network with short filaments(B) Fig: Reaction Force Vs Displacement of Network with long filaments(A)

0,5
Displacement(m)

1,5

Figure : Plot of Reaction Force Vs Displacement for of F-actin Network organized by long (A) and short (B) actin filaments

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1.14E+10 N m2

From the above analysis elasticity of the network A

2

with long filament comes out to be 3.38E+10 N while m the elasticity of the network B with long filament is

i.e. elasticity of the network A with long filament is

more compare to the network B with short filament The above model can be verified with similar type of model which is given by Lee, Ferrer ,Nakamura (8)

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They suggested that the reducing the length of the

individual filament lead to more loose ends in the configuration, thereby altering the network connectivity The resulting effect is that the network is less capable of withstanding stresses and therefore exhibit smaller modulus

Bibliography
1. (n.d.). Retrieved from Wikipedia: http://en.wikipedia.org/wiki/Cytoskeleton 2. Risler, T. (2011). Cytoskeleton and Cell Motility. 3. Abed, G. (2010). COMPUTATIONAL MECHANICS TOWARDS IMPROVED UNDERSTANDING OF THE BIOMECHANICS OF MYOCARDIAL INFARCTION. 4. David A. Head, A. J. (2003). Deformation of Cross-Linked Semiflexible Polymer Networks. PHYSICAL REVIEW LETTERS , 91 (10), 108102. 5. Frey, J. W. (2008). Elasticity of Stiff Polymer Networks. 6. X.-F. Wu, Y. A. (2005). Elasticity of planar fiber networks. JOURNAL OF APPLIED PHYSICS , 98, 093501. 7. R.Y. Kwon, A. L. (2008). A microstructurally informed model for the mechanical response of three-dimensional actin networks. Computer Methods in Biomechanics and Biomedical Engineering , 11 (4), 407418. 8. Hyungsuk Lee,Jorge M. Ferrer,Nakamura(2010). Acta Biometerialia,6,1207-1218 9. F. C. MacKintosh, J. K. (1995). Elasticity of Semiflexible Biopolymer Networks. P. A. Janmey , 75 (24).

Continued..
10.G. A. Buxton, N. C. (2009). Actin dynamics and the elasticity of cytoskeletal networks. eXPRESS Polymer Letters Vol.3, No.9 , 579-587. 11. Gardel, M. L. (2004). Elasticity of F-actin Networks. 12. Jeffrey S. Palmer, M. C. (2008). Constitutive modeling of the stress strain behavior of F-actin filament networks. Actabiomaterialia , 4, 597612. 13. Jonathan Stricker, T. F. (2010). Mechanics of the F-actin cytoskeleton. Journal of Biomechanics , 43, 914. 14. Madenci, E. (2005). The Finite Element Method and Applications in Engineering Using ANSYS (1st ed.). Springer. 15. Margaret L. Gardel, *. K. (2008). Mechanical Response of Cytoskeletal Networks. In M. L. Gardel, METHODS IN CELL BIOLOGY (Vol. 89, pp. 487-519). 16. ABAQUS CAE documentation. (n.d.). Retrieved from http://abaqus.civil.uwa.edu.au:2080/v6.9/

Thank You