In live cell imaging it is essential to analyze the pure motion of subnuclear proteins without influence of the cell nucleus motion and deformation which is referred to as nucleus global motion. In this work, we propose a 2D contour-based image registration approach for compensation of the global motion of the nucleus. Compared to a previous contour-based approach, our approach employs an explicit rigid registration step to compensate the nucleus translation and rotation, it uses morphological contour matching for establishing more reliable correspondences between contours in consecutive frames, and utilizes the Navier equation for more realistically modeling the nucleus deformation. Our approach was successfully applied to real live cell microscopy image sequences and an experimental comparison with an existing contour-based registration method and an intensity-based registration method has been performed.