Mechanical properties of crosslinked actin filament networks

Wang, Xiaobo 2020. Mechanical properties of crosslinked actin filament networks. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

As a substructure of cell cytoskeleton, the crosslinked actin filament networks (CAFNs) play a major role in different cell functions, however, the mechanical properties and the deformation mechanisms of CAFNs still remain to be understood. In this research, numerical simulations have been performed on a three-dimensional (3D) finite element (FE) model to mimic the mechanical properties of actin filament (F-actin) networks crosslinked by filamin A (FLNA). The simulation results indicate that although the Young’s moduli of CAFNs varies in different directions for each random model, the statistical mean value is in-plane isotropic. The crosslinking density and the actin filament volume fraction are found to strongly affect the in-plane shear modulus of CAFNs. In addition, a cantilever beam model is developed for dimensional analysis on the shear stiffness of CAFNs, which indicates that the in-plane shear modulus of CAFNs is mainly dominated by FLNA (i.e., crosslinkers). The dimensional analysis results agree well with the simulation results. In addition, the deformation mechanism of the CAFNs is also investigated by performing dimensional analysis and conducting numerical simulations. In physiological conditions, cells can undergo large deformation to respond to external stimulations and to support different cell functions. In large deformation situations, the CAFNs always show strong nonlinear elasticity to maintain the cell shape and integrity, which is known as strain stiffening. In this research, the nonlinear elastic properties of CAFNs are also studied by conducting numerical simulations. According to the results of numerical simulations, it can be demonstrated that the nonlinear elastic properties of crosslinked actin filament networks can be greatly influenced by the actin filament volume fraction, crosslinking density and components’ properties. The stress strain relationship of crosslinked actin filament networks is obtained and compared with experimental measurements reported in literature. In addition, the negative normal stresses of CAFNs are obtained from simulations, and the effects of the components’ properties on the negative normal stresses are discussed. In addition, to study the deformation mechanism of CAFNs in large strain regime, the effects of the components’ bending, torsional and tensile stiffnesses on the stress-strain curves of CAFNs are investigated. III Most of the biopolymer networks are proved to be viscoelastic and their mechanical properties are highly dependent on time and frequency. In physiological conditions, the viscoelastic behaviour of CAFNs could greatly affect the mechanical responses of cells, and different cell functions. Thus, it is important to study the viscoelasticity of CAFNs. The viscoelastic properties of actin filament networks crosslinked by filamin A are also investigated by conducting numerical simulations in this research. Both the creep and relaxation simulations are conducted in finite element method (FEM) software. In FEM simulations, different viscoelastic properties are applied to actin filament and FLNA respectively to probe their effects on the creep and relaxation behaviour of CAFNs. It is found that the FLNA affects the viscoelastic behaviour of CAFNs greater than actin filament. In addition, the effects of applied stress on the creep strain of CAFNs as well as the effects of applied strain on the relaxation stress of CAFNs are studied respectively. Simulation results also show that CAFNs with larger actin filament volume fraction creep less, however, larger actin filament volume fraction results in more relaxation in CAFNs. The creep strain and relaxation stress of CAFNs are found to reduce and increase with the actin filament volume fraction respectively. The crosslinking density is proved to have similar influences on the creep and relaxation behaviour of CAFNs. In addition, the dependence of dynamic shear modulus of CAFNs on the frequency and amplitude of applied loads are investigated. Results indicate that the storage shear modulus of CAFNs develops a plateau at low-frequency conditions, however, the loss shear modulus of CAFNs shows an increasing trend. At high-frequency conditions, both the storage and loss moduli of CAFNs scale with the frequency of applied loads. Moreover, the storage and loss shear moduli of CAFNs remain almost constant when the amplitude of applied load is small. However, they increase with the amplitude of applied load when the applied load reaches a critical value. The simulation results obtained in this research show good agreement with the experimental measurements and theoretical predictions reported in literature.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Engineering
Uncontrolled Keywords:	Mechanical properties; Actin filament network; Finite element model; Deformation mechanism; Dimensional analysis; Viscoelastic behaviour.
Date of First Compliant Deposit:	14 December 2020
Last Modified:	26 Oct 2021 01:37
URI:	https://orca.cardiff.ac.uk/id/eprint/137002

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