Quantitative analyses of cadherin-based cell-cell adhesive force
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Cell adhesion is a critical determinant of tissue architecture and tissue organization. Cadherin proteins mediate cell-cell adhesion in a calcium-dependent manner. The functional roles for cadherin proteins early in development and in adults, as well as the multiple disease phenotypes resulting from cadherin dysregulation, underscore the importance of cadherin proteins. Quantitative assessment of cadherin interaction structure, force, and interaction dynamics is not yet completely understood because of lack of experimental platforms to study cadherin proteins as well as their often-conflicting roles in a tissue-specific manner. Adhesive force measurements promise to meet this challenge of elucidating how cadherin complex assembly and function coheres in a spatiotemporal manner in human health and disease. The goal of this thesis was to engineer adhesive surfaces that support cadherin-based adhesion as a model system to analyze cadherin-dependent forces. We have engineered two different types of surfaces, based on self-assembly monolayers of alkanethiols on gold surfaces as well as micro-fabricated post-array detectors that present isolated and purified vascular endothelial cadherin ligands. The proposed research is significant because it focuses on creating a robust, quantitative experimental platform to study the formation of the cadherin complex in vitro and integrates a quantitative understanding of cell mechanics. Once validated, our approach will provide a strategy to understand the variables that promote the greatest adhesion strength.