A common geometric architecture for naturally occurring biomaterials is a hierarchical curvature and folding design that can be observed in a wide range of living systems such as the gyri in the brain or the microvilli on intestinal cells or the curved sporangia in fungi. Yet a fundamental understanding of the behavior of cells in relationship to this curvature and folding is lacking. This award seeks to self-assemble and characterize both synthetic and cell-derived composite hydrogels in biomimetic curved and folded geometries and characterize the behavior of the biomaterials and of the cells in these environments. Insights gained through this work may inform efforts to understand, support, and enhance development and recovery from injury in both the plant and the animal kingdoms. In addition to research, an emphasis will also be made on augmenting graduate education through curriculum changes, undergraduate and K-12 education through research experiences, as well as outreach to the local school system and enhancing excitement of biomaterials and tissue engineering to the broader public and society through lecture-demonstrations and joint projects with educators in the creative arts.
This award supports the creation and characterization of model bio-origami hydrogels composed of synthetic and cell-derived biomaterials, elucidation of the mechanisms for elevated activity of biochemical and small molecule production by cells in these geometries and investigation of the role of layering and fluidic gradients in curved and folded geometries during development, healing, and homeostasis. In the project, model hydrogel systems will be created so that the roles of folding pitch, curvature, three-dimensionality, and strain on cellular behavior can be individually isolated and interrogated. The methods used in this investigation will include the following: micro- and nano-patterning, three-dimensional structuring, strain engineering, material characterization, biochemical and cellular assays including in vitro reporters of signaling pathway activation and cytoskeletal reorganization, quantitative 3D image analysis and optical slicing, lattice light sheet microscopy, statistical design of experiments, and finite element modeling. This research program will catalyze multidisciplinary collaborative endeavor integrating cell biology and engineering, and create avenues for unique combinatorial training for graduate students in techniques and study designs that challenge the current state of the art.
