Graduate Defense: Madison Goldfeldt

Thesis Information

Title: A Computational Framework For Predicting Cell-Specific Nucleo-Cytoskeletal Forces In Mesenchymal Stem Cells

Program: Master of Science in Mechanical Engineering

Advisor: Dr. Gunes Uzer, Mechanical and Biomedical Engineering

Committee Members: Dr. Aykut Satici, Mechanical and Biomedical Engineering; and Dr. Clare Fitzpatrick, Biomedical Engineering

Abstract

Understanding the influence of mechanical forces on cell function and fate is crucial to unraveling the intricate mechanisms that govern cellular behavior. The cytoskeleton, a dynamic network of protein filaments, plays a pivotal role in sensing and transmitting mechanical cues within cells. The nucleus, in turn, relies on cytoskeletal mechanical input through nuclear envelope adaptor proteins to sense external stimuli and respond by regulating intra-nuclear chromatin organization. In studying and simulating the cellular response to mechanical forces this research aims to bridge the gap between mechanics and biology, uncovering the interrelation between physical forces and biochemical signaling. The developed computational framework reliably reconstructs nucleo-cytoskeletal morphology and computes cytoskeletal force on the nuclear surface via finite element (FE) analyses. Utilizing both manual and automated reconstruction techniques, the 3D nuclear geometry and relative location of F-actin stress fibers were extracted from confocal microscope images. This novel approach generates cell-specific FE models that incorporate two critical elements: i) F-actin configuration around the perinuclear region and ii) nuclear morphology to estimate nuclear envelope tension produced by the F-actin cytoskeleton.