Mechanical analysis of cortical tension and its interplay with cell adhesion in multicellular aggregates
Citation & Export
Hide
Simple citation
Moazzeni, Seyedsajad.
Mechanical analysis of cortical tension and its interplay with cell adhesion in multicellular aggregates. Retrieved from
https://doi.org/doi:10.7282/t3-n64s-rs14Export
Description
TitleMechanical analysis of cortical tension and its interplay with cell adhesion in multicellular aggregates
Date Created2023
Other Date2023-10 (degree)
Extent114 pages : illustrations
DescriptionThe interplay between tension and adhesion is a fundamental aspect of multicellular organisms, dictating the mechanical behavior of cell aggregates during tissue morphogenesis, cancer metastasis, and wound healing. However, the processes driving this dynamic interaction are not well-characterized nor quantified. This dissertation investigated the essential elements impacting cortical tension and its interaction with cell adhesion across various scales. This dissertation focuses on two important aspects of this subject and provides a comprehensive analysis of both. First, the mechanical behavior and cortical tension of single cells are analyzed using electrodeformation-relaxation. Four distinct cell types, namely, MCF-10A, MCF-7, MDA-MB-231, and GBM, are studied, with pulse durations ranging from 0.01 to 10 seconds. In the long-pulse regime, the mechanical response exhibits a power-law behavior, which indicates soft glassy rheology (SGR) resulting from unbinding events within the cortex network. On the other hand, the short-pulse regime is characterized by a single timescale, providing insights into the "naive" pre-stressed state of the cortex with minimal force-induced alterations. An analytical solution, supported by mathematical modeling is employed to extract the cortical tension. The tension values for all four cell types at the shortest pulse duration of 0.01 seconds are on the order of 10^-2 N/m. Second, the crucial role of N-cadherin in activating signaling pathways that result in "mechanical polarization" throughout the actin cortical network is elucidated. This polarization is characterized by increased cortical tension at the non-contacting boundary of cells and decreased interfacial tension at the cell-cell interface, both significantly contribute to adhesivestrength between cells. These tension regulations are found to induce remodeling in the F-actin cortex and strongly rely on the functionality of the non-muscle myosin II motor. Rac1 activation is identified as a molecular switch that regulates contraction in the actin cortex, providing a basic and general mechanism for tension regulation and aggregation control in solid tumors and spheroids. In summary, this dissertation provides a quantitative and contextual understanding of the complex mechanical interaction within multicellular organisms, shedding light on the fundamental factors that regulate cortical tension and collective behavior in clusters, aggregates, and tissues.
NotePh.D.
NoteIncludes bibliographical references
Genretheses
LanguageEnglish
CollectionSchool of Graduate Studies Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
Statistical Profile