Cell culture platforms with cell-cell adhesive ligands for biomedical applications

Cell behavior is regulated by a number of different mechanical and chemical cues within the extracellular microenvironment, including the surrounding matrix and neighboring cells. Although biomaterials have been engineered to present several adhesion molecules that mimic cell-extracellular matrix interactions, many materials do not consider the effects of cell-cell interactions. One such molecule is N-cadherin, a cell-cell adhesion protein which is expressed on both MSCs and neurons. N-cadherin regulates cytoskeleton organization, mechanotransduction, paracrine function, stem cell development, and neuronal growth. This molecule is an ideal candidate that can be incorporated into biomaterials to mimic cell-cell interactions. Recent efforts incorporated N-cadherin as well as other cell-cell adhesion proteins in hydrogel systems. However, the design of materials that effectively mimic N-cadherin interactions is not well-understood. With this in mind, my doctoral research examined the role of N-cadherin in modulating cell behaviors and the exploitation of these findings to design materials that regulate cell functions. Chapter 2 investigates the impact of different N-cadherin fragments on mesenchymal stem cell (MSC) mechanosensing and paracrine function. Chapter 3 explores how recombinant N-cadherin protein coated on different surfaces can instruct the formation of neural networks. Finally, Chapter 4 investigates the influence of N-cadherin on the secretion of exosomes, and their effects on stem cell differentiation and neuronal cultures. Together, these studies present the framework for building biomaterials that mimic cadherin-mediated cell-cell interactions in order to study stem cell mechanotransduction, to enhance paracrine function in the context of stem cell differentiation, and to improve the culture of neurons.LimitedAuthor requested closed access (OA after 2yrs) in Vireo ETD syste