Cell nucleus elastography with the adjoint-based inverse solver

TL;DR

This paper introduces an adjoint-based inverse solver to map the nonhomogeneous elastic properties of cell nuclei from microscopic deformation data, advancing nuclear elastography and understanding of cellular mechanics.

Contribution

The study presents the first application of an adjoint-based inverse method to identify spatially variable nuclear stiffness from microscopic deformation measurements.

Findings

Accurate identification of heterochromatin regions with less than 5% error.

Poisson's ratio variations cause less than 15% uncertainty in stiffness estimates.

Method applied successfully to real cell nuclei deformation data.

Abstract

Background and Objectives: The mechanics of the nucleus depends on cellular structures and architecture, and impact a number of diseases. Nuclear mechanics is yet rather complex due to heterogeneous distribution of dense heterochromatin and loose euchromatin domains, giving rise to spatially variable stiffness properties. Methods: In this study, we propose to use the adjoint-based inverse solver to identify for the first time the nonhomogeneous elastic property distribution of the nucleus. Inputs of the inverse solver are deformation fields measured with microscopic imaging in contracting cardiomyocytes. Results: The feasibility of the proposed method is first demonstrated using simulated data. Results indicate accurate identification of the assumed heterochromatin region, with a maximum relative error of less than 5%. We also investigate the influence of unknown Poisson's ratio on the reconstruction and find that variations of the Poisson's ratio in the range [0.3-0.5] result in uncertainties of less than 15% in the identified stiffness. Finally, we apply the inverse solver on actual deformation fields acquired within the nuclei of two cardiomyocytes. The obtained results are in good agreement with the density maps obtained from microscopy images. Conclusions: Overall, the proposed approach shows great potential for nuclear elastography, with promising value for emerging fields of mechanobiology and mechanogenetics.