An axisymmetric boundary integral model for incompressible linear viscoelasticity: application to the micropipette aspiration contact problem.

Abstract

The micropipette aspiration test has been used extensively in recent years as a means of quantifying cellular mechanics and molecular interactions at the microscopic scale. However, previous studies have generally modeled the cell as an infinite half-space in order to develop an analytical solution for a viscoelastic solid cell. In this study, an axisymmetric boundary integral formulation of the governing equations of incompressible linear viscoelasticity is presented and used to simulate the micropipette aspiration contact problem. The cell is idealized as a homogeneous and isotropic continuum with constitutive equation given by three-parameter (E, tau 1, tau 2) standard linear viscoelasticity. The formulation is used to develop a computational model via a "correspondence principle" in which the solution is written as the sum of a homogeneous (elastic) part and a nonhomogeneous part, which depends only on past values of the solution. Via a time-marching scheme, the solution of the viscoelastic problem is obtained by employing an elastic boundary element method with modified boundary conditions. The accuracy and convergence of the time-marching scheme are verified using an analytical solution. An incremental reformulation of the scheme is presented to facilitate the simulation of micropipette aspiration, a nonlinear contact problem. In contrast to the halfspace model (Sato et al., 1990), this computational model accounts for nonlinearities in the cell response that result from a consideration of geometric factors including the finite cell dimension (radius R), curvature of the cell boundary, evolution of the cell-micropipette contact region, and curvature of the edges of the micropipette (inner radius a, edge curvature radius epsilon). Using 60 quadratic boundary elements, a micropipette aspiration creep test with ramp time t* = 0.1 s and ramp pressure p*/E = 0.8 is simulated for the cases a/R = 0.3, 0.4, 0.5 using mean parameter values for primary chondrocytes. Comparisons to the half-space model indicate that the computational model predicts an aspiration length that is less stiff during the initial ramp response (t = 0-1 s) but more stiff at equilibrium (t = 200 s). Overall, the ramp and equilibrium predictions of aspiration length by the computational model are fairly insensitive to aspect ratio a/R but can differ from the half-space model by up to 20 percent. This computational approach may be readily extended to account for more complex geometries or inhomogeneities in cellular properties.