Date of Award
Fall 2023
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Engineering and Applied Science
First Advisor
Murrell, Michael
Abstract
Mechanical forces are essential in many life processes. The mechanical machinery of cells \textbf{--} the cytoskeleton is a complex system of force-bearing and active force-generation components. These components dynamically interact far from equilibrium in order to perform or facilitate biological functions at the cell scale such as shape change, migration, and polarization. Collectively, cells orchestrate single-cell mechanical functions to give rise to emerging mechanics at the tissue scale, such as embryo development or collective migration. Despite a good understanding of molecular mechanisms of force generation and force bearing, it is still unclear how molecular mechanics leads to cell-scale or tissue-scale phenomena. This remains a challenge that roots in the limitations of measuring forces within the cytoskeleton. By developing novel tools to measure intracellular forces, combined with mechanical characterization, measurement techniques, and continuum mechanics modeling, this thesis explores how actomyosin forces translate into higher-order functions and properties in single cells and simple tissues. At the single-cell level, our novel FRET-based tension sensor unveils load-bearing coordination between cortical and stress fibers leading to strain-dependent mechanical anisotropy. Mechanical anisotropy is essential for directional functions such as polarization and migration. The tension sensor further shows that strain-induced polarization relaxes the mechanical stresses. However, in confined cells, an increase in intracellular stresses translates to polarization and migration. At the tissue scale, we show that size-dependent surface tension constrains the pressure, volume, and density of cell spheroids. This establishes a unique equation-of-state for simple tissues. Using a combination of force measurement techniques and continuum modeling, we show that the unique mechanical properties of cell spheroids translate into emergent mechanisms of motion such as pressure-based spreading and Marangoni-like bulk flows. Throughout this thesis, we show how active force generation tunes the fundamental mechanical properties of cells and tissues. Besides finding similarities between the living systems and their passive analogs, we discover dissimilarities that mark a higher degree of complexity in the mechanics of living systems due to their non-equilibrium nature. This paves the way for establishing a framework for the mechanics of active matter.
Recommended Citation
AMIRI, SOROSH, "The Role of Mechanical Forces in Biological Motion and Morphology" (2023). Yale Graduate School of Arts and Sciences Dissertations. 1139.
https://elischolar.library.yale.edu/gsas_dissertations/1139
