Project Summary/Abstract
Within the biomedical field there is great effort to study a multitude of cell processes, including cell-cell
communication, cell-matrix interactions, cell signaling, pharmacological effects, and differentiation to name a
few. It is widely known that the more closely the cell culture system replicates the native cellular environment,
the more closely the cultured cells will model their native behaviors. Knowing this, over the years, various forms
of three-dimensional culture strategies have emerged as a superior advancement over 2D culture. The most
promising approaches include those that mimic the native extracellular matrix, in its architecture, mechanics,
and composition, thereby providing the ideal biological signaling and cellular recognition sites that promote
normal cell behavior. Towards this goal, the focus of this technology development proposal is to develop a
tunable, bioactive, DNA-based hydrogel platform that can meet these tissue specific requirements and serves to
advance in vitro cell culture. This material technology is significant because the DNA-based hydrogel platform
eliminates the need for complex chemical interactions and takes advantage of the rapid self-assembly and
spontaneous fibril formation that occurs when DNA is complexed with ECM protein collagen. In addition, this
platform utilizes functional DNA aptamers to render the hydrogel bioactive. This technology is poised to promote
cellular functions that are more native and reproducible to a broad community of biomedical researchers. To
achieve our goals, the aims of our project are 1) Examine to bulk material properties achievable with DNA-
collagen based hydrogels; and 2) Functionalize DNA-hydrogels with bioactive DNA aptamers. Our studies will
be compared to commonly used hydrogels and we will demonstrate biological impact through validation studies.
Completion of the above-described aims is expected to reveal the full breadth and potential of DNA-collagen
based materials to mimic tissue specific ECM and serve as a material platform for a broad array of biomedical
studies. We intend to develop a library of DNA-collagen bulk matrix with well-defined synthesis conditions
capable of tunable mechanical properties and bioactivity for a range of cell responses involved cell-cell
interactions, cell-matrix interactions, pharmacological studies, modelled health or disease states of cells,
mechanistic insight into varied cell phenotypes, stem cell studies, and an array of other fundamental studies of
tissue specific cell behaviors.