Mechanical Behaviors Of Cytoskeletal Networks

The cytoskeleton,a dynamic and intricate network of biopolymers and their associated cross-linking and motor proteins,is responsible for stabilizing cell shape as well as driving cell movement.The mechanical properties of a cell are largely determined by cytoskeleton,and the architecture of cytoskeletal networks relies on the assembly of actin with different cross-linking proteins.Actin monomers can be polymerized into double-stranded helical and semiflexible filaments(F-actin),aided by actin-binding proteins(ABPs),individual F-actin can be cross-linked into distinct types of actin structures,forming different cytoskeletal networks such as actin cortex,stress fibers,lamellipodium,and filopodium.Quantifying the deformation characteristics and load-bearing capabilities is the basis for understanding the biological functions of cells.In this paper,Monte Carlo method and Langevin dynamic simulations are used to investigate the dynamic behavior of growing actin networks and the mechanical response of randomly cross-linked semiflexible F-actins.The main contents of this thesis are summarized as follows.Growing actin networks provide the main driving force for the motility of cells and intracellular pathogens.Using Monte Carlo method,we developed a modeling framework based on the molecular-level process of actin polymerization,branching,capping,and depolymerization to simulate the stochastic and cooperative behaviors of growing actin networks in propelling obstacles,with an emphasis on the size and shape effects on work capacity and filament orientation in the growing process.Our results show that the characteristic size of obstacles changes the protrusion power per unit length,without influencing the orientation distribution of actin filaments in growing networks.In contrast,the geometry of obstacles has a profound effect on filament patterning,which influences the orientation of filaments differently when the drag coefficient of environment is small,intermediate,or large.We also discuss the role of various parameters,such as the aspect ratio of obstacles,branching rate,and capping rate,in affecting the protrusion power of network growthWe developed a computational model based on Langevin dynamics to examine the mechanical response of networks formed by randomly cross-linked filaments,where the bending and stretching of individual filaments,deformation,unbinding and rebinding of cross-linkers and the active role of molecular motors have all been considered.It was found that pronounced strain stiffening took place with increasing imposed shear deformation.However,such stiffening effect was attenuated by the successive rupture of cross-linkers.Interestingly,the appearance of motor-induced contractive forces within the networks significantly increased their apparent modulus in the entropy-dominated regime(i.e.,at small strain).Considerable bundling and re-alignment of filaments were also observed under the contraction by motor proteins,in agreement with experimental observations.In addition,the fluctuating forces generated by active motors were found to contribute to the enhanced diffusion of nanometer-sized particles within the network.We discussed the role of related factors,such as the polarity of individual filaments,the stiffness and length of cross-linkers,the length of individual F-actins and the contractile rate of active motors,in affecting the mechanical response of the networks.Rheology properties of the networks were also studied and our simulation results indicated that the behavior of permanently cross-linked networks under high oscillating frequency exhibits a universal power-law of 3/4 dependence for both storage modulus(G')and loss modulus(G")in the entropy-dominated regime.In contrast,at lower loading frequencies,the storage modulus(G')of the netowrks can be enhanced by the presence of contractile forces induced by molecular motors,while the loss modulus(G")is almost unaffectedIn this thesis,the dynamic behaviors of growing actin networks,the mechanical response of cytoskeletal networks formed by randomly cross-linked F-actins with/without active motors and intra-network transport of nanometer-sized particles were studied by numerical simulations.It provides the foundation for deep insights into the mechano-biological coupling mechanism of cytoskeletal structures in executing various biological functions,and the dynamic response of cells under various mechanical stimuli.