Abstract

Cells can adapt their mechanical properties through cytoskeleton remodelling in response to external stimuli when the cells adhere to the extracellular matrix (ECM). Many studies have investigated the effects of cell and ECM elasticity on cell adhesion. However, experiments determined that cells are viscoelastic and exhibiting stress relaxation, and the mechanism behind the effect of cellular viscoelasticity on the cell adhesion behaviour remains unclear. Therefore, we propose a theoretical model of a cluster of ligand–receptor bonds between two dissimilar viscoelastic media subjected to an applied tensile load. In this model, the distribution of interfacial traction is assumed to follow classical continuum viscoelastic equations, whereas the rupture and rebinding of individual molecular bonds are governed by stochastic equations. On the basis of this model, we determined that viscosity can significantly increase the lifetime, stability and dynamic strength of the adhesion cluster of molecular bonds, because deformation relaxation attributed to the viscoelastic property can increase the rebinding probability of each open bond and reduce the stress concentration in the adhesion area.

Highlights

  • As a salient characteristic in biological systems, cell adhesion plays a pivotal role in cell differentiation, migration and growth [1,2,3,4,5,6,7]

  • We developed an idealized viscoelastic–stochastic model of two elastic and viscoelastic bodies connected by a receptor–ligand bond cluster

  • We have performed Monte Carlo simulations to determine the role of cellular viscosity in biological behaviour of cell adhesion, such as lifetime, dynamic strength and stable window, by coupling the continuum deformation of the viscoelastic cell and elastic substrate and the stochastic behaviour of molecular bonds

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Summary

Introduction

As a salient characteristic in biological systems, cell adhesion plays a pivotal role in cell differentiation, migration and growth [1,2,3,4,5,6,7]. From the physics point of view, cells are typically viscoelastic materials and the deformation of cells depends on loading history [57], which has been investigated extensively with a variety of quantitative experimental methods, including atomic force microscopy [58], magnetic bead micro-rheometry [59], magnetic micro-needle [60], traction force microscopy [61] and optical tweezers [62] These experiments highlighted that the local cellular mechanical properties exhibit distinct viscoelasticity, which can be generally regarded as Kelvin-type material with the viscosity in the range from tens to thousands of Pa s. We attempt to address the above problem by proposing a coupled viscoelastic–stochastic model of the cell with viscoelastic properties adhering to an elastic substrate under an external applied force, considering that the mechanism of the effect of cellular viscoelasticity on adhesion behaviour remains unclear. Consider the closed receptor–ligand bond as a linear spring with stiffness kLR, rest length lb and reacting radius lbind around the binding site

Stress relaxation-dependent interfacial traction
Stochastic dynamics of single receptor–ligand bonds
Stochastic–viscoelastic coupling through Monte Carlo simulation
Results and discussions
Effects of cellular viscosity on the dynamic strength of bond cluster
Effects of cellular viscosity on the window of stable adhesion
Conclusion

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