Assessment of the mechanical properties of the nucleus inside a spherical endothelial cell based on microtensile testing

Deguchi, Shinji; Yano, Masayuki; Hashimoto, Ken; Fukamachi, Hiroyuki; Washio, Seiichi; Tsujioka, Katsuhiko

doi:10.2140/jomms.2007.2.1087

Cited by 21 publications

(24 citation statements)

References 36 publications

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“…We remark that, rigorously speaking, the length of contact slightly changes during nucleus entrance into the channel. However, considering a cell of radius 15 µm [12] with nuclear radius equal to 5 µm [12,37], the discrepancy between L f in b , which is the length of contact in the final deformed configuration (see Fig. 1(b)), and L b , the length of contact in the initial condition, is less than 1%.…”

Section: Cytoskeleton Active Work For a Single Cellmentioning

confidence: 93%

How Nucleus Mechanics and ECM Microstructure Influence the Invasion of Single Cells and Multicellular Aggregates

2017

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In order to move in a three-dimensional extracellular matrix, the nucleus of a cell must squeeze through the narrow spacing among the fibers and, by adhering to them, the cell needs to exert sufficiently strong traction forces. If the nucleus is too stiff, the spacing too narrow, or traction forces too weak, the cell is not able to penetrate the network. In this article, we formulate a mathematical model based on an energetic approach, for cells entering cylindrical channels composed of extracellular matrix fibers. Treating the nucleus as an elastic body covered by an elastic membrane, the energetic balance leads to the definition of a necessary criterion for cells to pass through the regular network of fibers, depending on the traction forces exerted by the cells (or possibly passive stresses), the stretchability of the nuclear membrane, the stiffness of the nucleus, and the ratio of the pore size within the extracellular matrix with respect to the nucleus diameter. The results obtained highlight the importance of the interplay between mechanical properties of the cell and microscopic geometric characteristics of the extracellular matrix and give an estimate for a critical value of the pore size that represents the physical limit of migration and can be used in tumor growth models to predict their invasive potential in thick regions of ECM.

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Section: Cytoskeleton Active Work For a Single Cellmentioning

confidence: 93%

How Nucleus Mechanics and ECM Microstructure Influence the Invasion of Single Cells and Multicellular Aggregates

2017

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“…Various experiments have been designed to understand effects of the subcellular components on the local 15,22,24 and entire mechanical properties of cells. 1,4,10,11,13,18 Although these studies have provided valuable information for understanding cell mechanics, the heterogeneous intracellular structures often cause difficulties in interpreting experimental results.…”

Section: Introductionmentioning

confidence: 99%

“…Assuming that the smallest length scale of interest is much larger than the dimensions of the microstructure, continuum mechanics have been widely used to describe how strains and stresses distribute within a cell. 4,7,19 The disadvantage of continuum model lies in dealing with discrete components such as cytoskeletons, making it difficult to interpret the contributions of discrete components to cell mechanics. As an alternative, discrete models are used to describe the mechanical stability of a cell, consisting of a particular structure and subcellular component composition.…”

Section: Introductionmentioning

confidence: 99%

Proposed Spring Network Cell Model Based on a Minimum Energy Concept

et al. 2010

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We developed a mechano-cell model incorporating a cell membrane, a nuclear envelope, and actin filaments to simulate the mechanical behavior of a cell during tensile tests. The computational model depicts a cell as a combination of various spring elements in the framework of the minimum energy concept. A cell membrane and a nuclear envelope are both modeled as shells of a spring network that express elastic resistance to changes in bending, stretching, and surface area. A bundle of actin filaments is represented by a mechanical spring that generates a force as a function of its extension. The interaction between the nuclear envelope and the cell membrane is expressed by a potential energy function with respect to the distance between them. Incompressibility of a cell is assured by a volume elastic energy function. The cell shape during a tensile test is determined by a quasi-static approach, such that the total elastic energy converges to the minimum. The load-deformation curve obtained from the simulation shows a significant increase in stretching load with deformation of the cell and lies within a range of experimentally obtained load-deformation curves. The total elastic energy is dominated by the energy stored in the actin fibers. Actin fibers that are randomly oriented before loading tend to become aligned, passively, in the stretched direction. These results attribute the non-linearity in the load-deformation curve to passive reorientation of actin fibers in the stretched direction.

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“…We have not explored in detail dependence of the motile behavior on mesh size and adhesion characteristics. The ECM, cortex and nucleus in our model are a linear elastic network, while the mechanical properties of actual ECM, cortex and nucleus are very complex [32,53]. Needless to say, we have not investigated how cells change migration mode in response to the ECM properties [54], and we have not considered other modes of motility, such as blebbing [30] and chimneying [55].…”

Section: Discussionmentioning

confidence: 99%

“…Physical parameters: Geometric parameters include the ECM mesh size and sizes of the cell cortex and nucleus, which are all of the same order of magnitude [5,32]: cell diameter is of the order of 10 µm, while the nuclear diameter is slightly smaller [33]. Openings in 3D extracellular environments range from 2 to 30 µm in diameter [34].…”

Section: Parameter Values and Numerical Proceduresmentioning

confidence: 99%

Computational estimates of mechanical constraints on cell migration through the extracellular matrix

Maxian

Mogilner

Strychalski

2020

Preprint

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Cell migration through three-dimensional (3D) extracellular matrix (ECM) underlies important physiological phenomena and is based on a variety of mechanical strategies depending on the cell type and the properties of the ECM. By using computer simulations, we investigate two such migration mechanisms -'push-pull' (forming a finger-like protrusion, adhering to an ECM node, and pulling the cell body forward) and 'rear-squeezing' (pushing the cell body through the ECM by contracting the cell cortex and ECM at the cell rear). We present a computational model that accounts for both elastic deformation and forces of the ECM, an active cell cortex and nucleus, and for hydrodynamic forces and flow of the extracellular fluid, cytoplasm and nucleoplasm. We find that relations between three mechanical parameters -the cortex's contractile force, nuclear elasticity and ECM rigidity -determine the effectiveness of cell migration through the dense ECM. The cell can migrate persistently even if its cortical contraction cannot deform a near-rigid ECM, but then the contraction of the cortex has to be able to sufficiently deform the nucleus. The cell can also migrate even if it fails to deform a stiff nucleus, but then it has to be able to sufficiently deform the ECM. Simulation results show that nuclear stiffness limits the cell migration more than the ECM rigidity. Simulations of the rear-squeezing mechanism of motility results in more robust migration with larger cell displacements than those with the push-pull mechanism over a range of parameter values. Author summaryComputational simulations of models representing two different mechanisms of 3D cell migration in an extracellular matrix are presented. One mechanism represents a mesenchymal mode, characterized by finger-like actin protrusions, while the second mode is more amoeboid in that rear contraction of the cortex propels the cell forward. In both mechanisms, the cell generates a thin actin protrusion on the cortex that attaches to an ECM node. The cell is then either pulled (mesenchymal) or pushed (amoeboid) forward. Results show both mechanisms result in successful migration over a range of simulated parameter values as long as the contractile tension of the cortex exceeds either the nuclear stiffness or ECM stiffness, but not necessarily both. However, January 20, 2020 1/25 the distance traveled by the amoeboid migration mode is more robust to changes in parameter values, and is larger than in simulations of the mesenchymal mode. Additionally cells experience a favorable fluid pressure gradient when migrating in the amoeboid mode, and an adverse fluid pressure gradient in the mesenchymal mode.

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Assessment of the mechanical properties of the nucleus inside a spherical endothelial cell based on microtensile testing

Cited by 21 publications

References 36 publications

How Nucleus Mechanics and ECM Microstructure Influence the Invasion of Single Cells and Multicellular Aggregates

How Nucleus Mechanics and ECM Microstructure Influence the Invasion of Single Cells and Multicellular Aggregates

Proposed Spring Network Cell Model Based on a Minimum Energy Concept

Computational estimates of mechanical constraints on cell migration through the extracellular matrix

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