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ARUP; ISBN: 978-0-9562121-5-3 - CMBBE 2012 - Cardiff University

ARUP; ISBN: 978-0-9562121-5-3 - CMBBE 2012 - Cardiff University

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geometry of the cell and ECM degradation can independently impact the movement of<br />

cells. In this study, we examined a model that follows the approach of Harjanto and<br />

Zaman [6], and investigated how cell shape and size can independently influence<br />

mesenchymal cell migration. Focal adhesion mechanical properties that were<br />

independent or dependent on cell shape were considered.<br />

3. METHODS<br />

The geometry of the cell was modeled as an ellipsoid. The semi-axis of the cell that was<br />

aligned with the direction of motion was given by bcell and acell was used to refer to the<br />

semi-axes in the transverse directions. Since the model was axisymmetric with respect<br />

to the centerline of the cell (r = 0) that was parallel to the direction of cell motion (zdirection),<br />

only half of an ellipse was constructed in COMSOL Multiphysics 4.2.<br />

Rotating this 2D slice with respect to r = 0 would result in the ellipsoid. A schematic of<br />

the different geometries is provided in Fig. 1.<br />

Figure 1. Schematic of the cell geometry and traction distribution for the case where<br />

(a) fcell = bcell/acell = 2 or (b) fcell = 0.5.<br />

The expressions for the cell–ECM traction and drag forces applied on the surface of the<br />

cell as well as the equation that governed the degradation of the matrix followed the<br />

approach we described earlier in [9]. For the present study, we computed an adhesion<br />

coefficient of βadh = 600 nm 2 /molecule by using 0.6 as the ratio of traction to substrate<br />

stiffness [10] and an average bound receptor cell surface concentration of 1,000<br />

molecule/µm 2 . The initial receptor and substrate cell surface concentrations were set at<br />

10,000 molecule/µm 2 in the simulations [11], and the Young’s modulus of the cell was<br />

1 kPa. All of the other parameters were the same as those given in our earlier paper [9].<br />

Simulations were used to study the effects of the cell shape and size on cell migration as<br />

the ECM degradation coefficient (α) was varied. The aspect ratio of the cell,<br />

fcell = bcell/acell, was used to characterize the cell shape, and the values that used were<br />

fcell = 0.5, 0.75, 1, 1.5, and 2. In this set of simulations, the cross-sectional area of the<br />

cell was kept constant and equal to that where acell = bcell = 25 µm, which was<br />

1,963.5 µm 2 . The traction was normal to the cell surface in each case [10]. A schematic<br />

of the traction distributions for different cell shapes can be seen in Fig. 1. It was<br />

assumed that βadh = 600 nm 2 /molecule for fcell = 1, and the adhesion coefficient was<br />

increased with bcell using the data reported by Rape, et al. where it was shown that cell<br />

shape influences adhesions and tractions [12]. For comparison purposes, simulations<br />

were also conducted for the case where the adhesion coefficient was fixed at

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