Mechanical Properties Of Cytoskeleton Research Articles

Linear and nonlinear mechanical responses of cell monolayers under crowding

Epithelial monolayers play an important role in a broad range of physiological and pathological processes, such as embryonic development and wound healing. Epithelial monolayers become crowded during cell proliferation and growth, however, their mechanical properties entities remain obscure. This paper presents a novel and efficient method utilizing the structural stiffness matrix-based computational method (SMM) to investigate the mechanical characteristics of an epithelial monolayer as it undergoes varying degrees of crowding. Both D1-type extrusion, representing the extrusion of live cells, and D2-type extrusion, describing the extrusion of apoptotic cells, are examined. Our simulations reveal that the epithelial monolayer exhibits linear elastic behavior under slight crowding and nonlinear elastic behavior in response to overcrowding. These mechanical properties are significantly influenced by the strength of cellular cytoskeleton and the mode of cell extrusion. Moreover, our analysis indicates that the linear deformation of these monolayers is predominantly born by the variation in cell orientation, while the nonlinear deformation originates from the existence of the microtubules. This study further deepens our understanding of the relationship between the mechanical properties of cytoskeleton, individual cells and their monolayers, and may shed light on linking cell behavior to the patterning and morphogenesis of tissues.

Mechanics of actin filaments in cancer onset and progress.

Cancer, as a major cause of mortality, is highly related to alterations in the structure and behavior of cells of cancerous tissues. The invasive nature of cancer cells is correlated with their increased traction force, high deformability and altered cell adhesion. These changes are directly attributed to the remodeling of cell cytoskeleton mostly in actin structure. While microtubules and intermediate filaments are mostly involved in mechanical properties of cytoskeleton, actin fibers actively contribute to not only mechanical properties, but also other aspects. Hence study of actin mechanics assists in a deeper understanding of cancer related events. Here, with a biomechanical perspective, we describe the cytoskeleton changes in cancer onset and progress in fiber and protein levels, with focus on actin structure in terms of content and arrangement. Cytoskeleton remodeling and particularly alterations in the content and arrangement of actin structure, highly influence cell mechanical properties, force generation and adhesion potentials.

The effect of cellular volume regulation on cell physiological functions

As an open system, cells can exchange water, ions and energy with the environment, thus the cellular volume and pressure are not constant. In the last decade, cellular volume regulation has attracted intense attention. It has been found that the changes of cell volume can impact many cell physiological processes, such as cell mechanical properties, cell metabolic activities, cell viability and cell growth. However, the mechanisms of cellular volume regulation and how the changes of cell volume affect cell physiological functions are still unclear. In this paper, we will briefly review the mechanisms of cellular volume and pressure regulation, as well as the roles of cellular volume regulation in cancer cell migration, cell adhesion and cell mechanics. The regulation of cellular volume includes the combined effects of the transport of water and ions, as well as the mechanical properties of cytoskeleton. The membrane is permeable to water and the flow of water is driven by the osmotic pressure difference and the hydrostatic pressure difference across the membrane. Since water is incompressible, the transport of water is directly related to the changes in cellular volume. And cells can regulate the ion number (the osmotic pressure) inside the cells by the ion efflux through ion channels and ion pumps. The properties of cytoskeleton can control the activity of ion channels, and then affect the cellular volume regulation. Experiments found that when cells migrate in narrow channels, they can undergo persistent movement in one direction for several hours, and this persistent movement occurs spontaneously in the absence of external gradients. Inhibition of adhesion complexes and cortical contractility do not affect cell migration in narrow channels. In contrast, the adhesion complexes and cortical contractility are the prerequisite of the cell migration on two dimensional substrates since they can provide the traction force for cell migration. Recent theoretical studies and experiments have showed that the water permeation through the cell membrane at leading and trailing edges can provide the driving force for the cell migration in the 3D confined microenvironments. Furthermore, the changes in cell volume can affect the morphology and mechanics of cells adhered between two surfaces. Depending on the cell size, adhesion energy density, the separation of two adhesive surfaces, and the stiffness of the flexible surface, cells can be convex or concave. Furthermore, the changes in volume can directly lead to two unstable adhesion states, i.e., spontaneous rupture and collapse. The changes in cell volume can also affect the detachment of adherent cells. Different changes in cell volume would lead to different detachment behavior for convex cells and concave cells. The cell volume of convex cells decreases during detachment, which is accompanied by a decrease in stretch force. However, the volume of concave cells increases during detachment, and then leads to an increase in stretch force. Moreover, as an open system, the mechanical responds of cells is related to the loading history and the loading rate. This review summaries the mechanisms of cellular volume regulation, emphasizes the importance of water and ion transport in cellular volume regulation, and discusses the regulating roles of cellular volume changes in cancer cell migration, cell adhesion and cell detachment. In conclusion, this review provides an overview of the experimental and theoretical developments on cellular volume regulation, and discusses the current challenges and further prospects of how cellular volume changes affect the cell physiological processes, such as wound healing, cell spreading, membrane trafficking, rigidity sensing, haptotaxis, durotaxis and cell fate determination.

Spatial Distribution of Cytoskeletal Mechanical Properties in Vascular Smooth Muscle Cells

The mechanical properties on a whole basis of cell are extensively studied whereas regional mechanical properties of the cytoskeleton (CSK) have not been characterized. To fill this gap, here we provide detailed intracellular maps of regional CSK stiffness and traction forces, as well as the structural rearrangement in vascular smooth muscle cells (VSMCs). We used micropatterning to restrict VSMC to a single island. Regional cell stiffness was measured with optical magnetic twisting cytometry and traction force microscopy was used to measure regional traction forces. Finally, we used F-actin staining to measure the regional F-actin distribution. From traction and cell height data we computed the prestress within a cell using finite element methods. Compared with the cell center, cell edges were systematically stiffer, more fluid-like and supported higher traction forces, and at the same time had slower remodeling dynamics. These findings provide the most detailed characterization to date concerning regional mechanical properties of the intact cytoskeleton.

Elastic Properties of Actin Assemblies in Different States of Nucleotide Binding

In this paper, the elastic properties of monomeric actin (G-actin) and the trimer nucleus (G-actin trimer) in different states of nucleotide binding are estimated using steered molecular dynamic (SMD) simulations. Three nucleotide binding states are considered: ADP- and ATP-bound actin and nucleotide-free actin assemblies. Our results show that nucleotide binding and the corresponding changes in structure have significant effects on the mechanical behaviors of actin assemblies. Simulations reveal that the deformation behavior of G-actin monomers is generally elastic up to engineering strains of 16 and 40% in the tension and shear tests, respectively. In addition, the G-actin trimers react linearly up to strains of 18%. The computed persistence lengths for G-actin monomers and trimers are in the range of 8–20 μm, which are consistent with earlier experimental results. Our atomistic simulation results also reveal that formation and rupture of hydrogen bonds between actin nucleotide binding site and its nucleotide have significant role in response of actin assemblies to loading. This study provides more information about the relationship of actin nucleotide binding and mechanical properties of cytoskeleton.

112 細胞骨格と核の力学特性の計測

112 細胞骨格と核の力学特性の計測