A viscoelastic–stochastic model of the effects of cytoskeleton remodelling on cell adhesion

Li, Long; Zhang, Wenyan; Wang, Jizeng

doi:10.1098/rsos.160539

Cited by 21 publications

(12 citation statements)

References 89 publications

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“…Cylindrical NPs and membrane surface tension are not considered. Kinetic reaction between receptor and ligand molecules [ 32 , 46 , 52 – 54 ], and viscoelastic deformation of cytoskeleton [ 23 , 55 ] are neglected.…”

Section: Discussionmentioning

confidence: 99%

Effects of ligand distribution on receptor-diffusion-mediated cellular uptake of nanoparticles

Li¹,

Zhang²,

Wang³

2017

R. Soc. open sci.

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Biophysical-factor-dependent cellular uptake of nanoparticles (NPs) through receptor-diffusion-mediated endocytosis bears significance in pathology, cellular immunity and drug-delivery systems. Advanced nanotechnology of NP synthesis provides methods for modifying NP surface with different ligand distributions. However, no report discusses effects of ligand distribution on NP surface on receptor-diffusion-mediated cellular uptake. In this article, we used a statistical dynamics model of receptor-diffusion-mediated endocytosis to examine ligand-distribution-dependent cellular uptake dynamics by considering that ligand–receptor complexes drive engulfing to overcome resistance to membrane deformation and changes in configuration entropy of receptors. Results showed that cellular internalization of NPs strongly depended on ligand distribution and that cellular-uptake efficiency of NPs was high when ligand distribution was within a range around uniform distribution. This feature of endocytosis ensures robust infection ability of viruses to enter host cells. Interestingly, results also indicated that optimal ligand distribution associated with highest cellular-uptake efficiency slightly depends on distribution pattern of ligands and density of receptors, and the optimal distribution becomes uniform when receptor density is sufficiently large. Position of initial contact point is also a factor affecting dynamic wrapping. This study explains why most enveloped viruses present almost homogeneous ligand distribution and is useful in designing controlled-release drug-delivery systems.

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Section: Discussionmentioning

confidence: 99%

Effects of ligand distribution on receptor-diffusion-mediated cellular uptake of nanoparticles

Li¹,

Zhang²,

Wang³

2017

R. Soc. open sci.

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“…In the cytoskeleton system, the filamentous actin (F-actin) (Figure 1) is one of the most major constituent building up many higher order structures in cells (e.g., stress fibers, lamellipodia, and filopodia) [8]. The arrangement and distribution of F-actin greatly dominates the mechanical properties of cells including viscoelasticity [9][10][11][12][13]. For example, the actin cortex is a thin layer that lies beneath the plasma membrane, maintaining and regulating cell topography [10].…”

Section: Introductionmentioning

confidence: 99%

“…The stress fibers are arranged in parallel by F-actin, connecting the cytoskeleton to the extracellular matrix via focal adhesions [12]. Wang et al reported that viscosity of F-actin can significantly increase stability of the cell adhesion [13]. The cellular protrusions including lamellipodium and filopodium located at the edge of cells is involved with the cell migration [14,15].…”

Section: Introductionmentioning

confidence: 99%

Effect of F-Actin Organization in Lamellipodium on Viscoelasticity and Migration of Huh-7 Cells Under pH Microenvironments Using AM-FM Atomic Force Microscopy

et al. 2021

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Cytoskeleton is responsible for fundamental cellular processes and functions. The filamentous actin (F-actin) is a key constituent of the cytoskeleton system which is intrinsically viscoelastic and greatly determines the mechanical properties of cells. The organization and polymerization of F-actin are relevant to the viscoelasticity distribution and the migration of living cells responding to pH microenvironments. Recently, progression in various diseases such as cancers have been found that cellular migration is related to the alterations in the viscoelasticity of lamellipodium. However, the correlation among F-actin organization, viscoelastic properties and cellular migration of living cancer cells under different pH microenvironments are still poorly understood. Conventional experimental methods of optical microscopy and atomic force microscopy (AFM) can neither break the trade-off between resolution and rate in cytoskeleton imaging, nor achieve the structural characterization and the mechanical measurement simultaneously. Although multifrequency AFM with amplitude modulation-frequency modulation (AM–FM) enables us to probe both the surface topography and the viscoelasticity distribution of cells, it is difficult to image the cytoskeletal filaments with the diameter down to the scale of tens of nanometers. Here, we have improved the AM-FM AFM by employing the high damping of cell culture medium to increase the signal-to-noise ratio and achieve a stable imaging of F-actin with the resolution down to 50 nm under in situ microenvironment. The approach that can successfully visualize the structures of cytoskeletal filaments and measure the distribution of mechanical properties simultaneously enable us to understand the relationship between the organization of F-actin and the viscoelasticity of living Huh-7 cancer cells under different pH values. Our experimental results have demonstrated that, unlike the randomly distributed F-actin and the homogeneous viscoelasticity at the normal pH level of 7.4, the living Huh-7 cancer cells with the reduced pH level of 6.5 show highly oriented and organized F-actin along the lamellipodium direction associated with the significant gradient increase both in elasticity and viscosity, which are confirmed by immunofluorescence confocal microscopy. The F-actin organization and the gradient viscoelasticity of lamellipodium provide structural and mechanical understanding on the adhesion and migration of living cancer cells that undergo metastasis and malignant transformation.

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“…Subsequently, two-pathway models of catch bond have been proposed to describe the kinetic reaction of catch-bond dissociation [11][12][13]. In addition to the chemical reactions of receptor-ligand bonds, the effect of other physical and mechanical factors, such as loading condition [14][15][16][17], deformation of substrate [18][19][20][21][22][23][24][25], membrane fluctuation [26][27][28][29], multiple bonds [30,31], cluster size [32], and cytoskeletal contraction [33,34] on cell or membrane adhesion have been discussed extensively. However, these studies focus on the occurrence of adhesion in a relatively quiescent environment.…”

Section: Introductionmentioning

confidence: 99%

Mechanical Model for Catch-Bond-Mediated Cell Adhesion in Shear Flow

Kang

Wang

2020

IJMS

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Catch bond, whose lifetime increases with applied tensile force, can often mediate rolling adhesion of cells in a hydrodynamic environment. However, the mechanical mechanism governing the kinetics of rolling adhesion of cells through catch-bond under shear flow is not yet clear. In this study, a mechanical model is proposed for catch-bond-mediated cell adhesion in shear flow. The stochastic reaction of bond formation and dissociation is described as a Markovian process, whereas the dynamic motion of cells follows classical analytical mechanics. The steady state of cells significantly depends on the shear rate of flow. The upper and lower critical shear rates required for cell detachment and attachment are extracted, respectively. When the shear rate increases from the lower threshold to the upper threshold, cell rolling became slower and more regular, implying the flow-enhanced adhesion phenomenon. Our results suggest that this flow-enhanced stability of rolling adhesion is attributed to the competition between stochastic reactions of bonds and dynamics of cell rolling, instead of force lengthening the lifetime of catch bonds, thereby challenging the current view in understanding the mechanism behind this flow-enhanced adhesion phenomenon. Moreover, the loading history of flow defining bistability of cell adhesion in shear flow is predicted. These theoretical predictions are verified by Monte Carlo simulations and are related to the experimental observations reported in literature.

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A viscoelastic–stochastic model of the effects of cytoskeleton remodelling on cell adhesion

Cited by 21 publications

References 89 publications

Effects of ligand distribution on receptor-diffusion-mediated cellular uptake of nanoparticles

Effects of ligand distribution on receptor-diffusion-mediated cellular uptake of nanoparticles

Effect of F-Actin Organization in Lamellipodium on Viscoelasticity and Migration of Huh-7 Cells Under pH Microenvironments Using AM-FM Atomic Force Microscopy

Mechanical Model for Catch-Bond-Mediated Cell Adhesion in Shear Flow

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