In order to systematically dissect the dynamic biophysical interactions between cells and the matrix, it is necessary to develop experimental platforms where each of the components in the system can be independently and spatiotemporally manipulated. This has been the focus of our work, and we specifically address this at different levels of complexity. We have developed and characterized platforms that allows (1) microscale manipulation of the spatial location of ligands in the cell substrate, (2) on-demand manipulation of the non-planar structure of cell substrates, and (3) longitudinal manipulation of tissue and organoid formation. In addition, we have also developed analytical tools that will be used to analyze cell and tissue functionalities in these constructs.
Using these developed tools, we studied the role of dynamic cell-matrix interactions in cell and tissue functions, focusing on a few physiologically relevant phenomena. First, we demonstrated that the phenotype transition of fibroblasts – a cell type critical in wound healing, tissue maintenance, and homeostasis – is modulated by spatial organization of ligands in the substrate as well as the dynamic changes in the substrate geometry. This occurs through a mechanoadaptation mechanism that is mediated by the cells’ adhesion, cytoskeletal rearrangement, and nucleus localization. Furthermore, we showed that the interplay between cell-cell and cell-matrix interactions is important for cell’s mechanosensitivity to external cues such as dynamic strain, topography, and constraints. By manipulating these physical cues, it is possible to influence cell differentiation, organization, and even tissue formation.
These developments and findings have been reported in several peer-reviewed journal publications and presented in international conferences and meetings. We are currently pursuing this research direction further and are planning to apply for additional funding to extend the work.
