A Computational Framework to Model Mesenchymal Stem Cell Nucleus Mechanics Using Confocal Microscopy
Date of Final Oral Examination (Defense)
Type of Culminating Activity
Master of Science in Mechanical Engineering
Mechanical and Biomechanical Engineering
Gunes Uzer, Ph.D.
Clare Fitzpatrick, Ph.D.
Mahmood Mamivand, Ph.D.
The mechanical properties of the cell nucleus are emerging as a key component in genetic transcription. It has been shown that the stiffness of the nucleus in part regulates the transcription of genes in response to external mechanical stimuli. The stiffness has been shown to change as a result of both disease and changes to the external environment. While the mechanical structure of the nucleus can be visually documented using a confocal microscope, it is currently impossible to test the stiffness of the nucleus without a mechanical testing apparatus such as an atomic force microscope. This is problematic in that the use of a mechanical testing apparatus involves deconstructing the cell in order to isolate the nucleus and is unable to provide data on internal heterochromatin dynamics within the nucleus. Therefore, our research focused on developing a computational framework that would allow researchers to model the mechanical contributions of the nucleus specific geometry and material dispersion of both chromatin and LaminA/C within an individual nucleus in order to improve the ability of researchers to study the nucleus. We began by developing a procedure that could generate a finite element geometry of a nucleus using confocal images. This procedure was then utilized to generate models that contained elasticity values that corresponded to the voxel intensities of images of both chromatin and LaminA/C by using a set of conversion factors to link image voxel intensity to model stiffness. We then tuned these conversion factors by running in silico atomic force microscopy experiments on these models while comparing the simulation results to atomic force microscopy data from real world nuclei. From this experiment we were able to find a set of conversion factors that allowed us to replicate the external response of the nucleus. Our developed computational framework will allow future researchers to study the contribution of multitude of sub-nuclear structures and predict global nuclear stiffness of multiple nuclei based on confocal images and AFM tests.
Kennedy, Zeke, "A Computational Framework to Model Mesenchymal Stem Cell Nucleus Mechanics Using Confocal Microscopy" (2020). Boise State University Theses and Dissertations. 1737.