NSF2026: EAGER: Harnessing Protein Disorder in the Design of Ordered Cellular Materials

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Non-technical summaryWith support from the Biomaterials Program of the NSF Division of Materials Research, and the NSF 2026 Fund Program in the Office of Integrated Activities, Professors Das and Kiik at University of Delaware are awarded for their proposal "Harnessing Protein Disorder in the Design of Ordered Cellular Materials". The research involves the fact that synthetic biological materials must include “smart” functional properties – self-regulation, self-healing, environmental responsiveness, and self-sustainability – to function as engineered living materials (ELMs), which are poised to revolutionize present-day materials technologies. ELMs can offer insights into the development of living organs, the organization of multiple organ systems, and the production of autonomously sensing and healing materials. However, the large-scale manufacture of engineered living materials has been difficult to achieve, owing to a lack of control of both materials’ organization and cell and molecule placement over multiple length scales. This proposal addresses this gap by developing microstructured hydrophilic polymer hydrogels. The polymer solutions used in this proposal have the unique capability of reversibly changing concentration in the presence of specific compounds, which will allow the use of micron-scale robots to deliver these compounds to produce patterned hydrogels. These approaches will be integrated with cells to generate highly ordered cell-gel materials with high cell viability. The precise and programmable spatial control of hydrogel properties will enable localized differentiation of stem cells to form engineered living materials, and subsequent manufacture of complex tissues for advancing national health. The project includes a plan to engage K-12 girls and their caregivers in hands-on robotics activities that will enhance learning strategies and stimulate interest in science and engineering. Graduate and undergraduate students will receive training in an interdisciplinary environment blending materials science and robotics.Technical summaryThe proposed research will develop a new approach for making addressable, microrobotically-controlled engineered living materials (ELMs) with functional properties. The large-scale manufacture of ELMs requires the reliable control of both materials’ organization and cell and molecule placement over multiple length scales. The overarching goal of this proposal is to generate polymer hydrogels with regular microstructured regions of distinct mechanical properties, based largely on resilin-like polypeptides (RLPs) derived from the bioelastomer resilin. RLP-based solutions have the unique capability of reversibly changing concentration in the presence of small-molecule and polymeric co-solutes. The working hypothesis in this proposal is that the microrobotic delivery of polyethylene glycol (PEG) will rapidly trigger a locally increased concentration of RLPs near microrobots, leading to the formation of mechanically distinct microstructured regions in the bioelastomer. The coincident use of a digital micromirror display (DMD) system will permit the co-localization of light, thus initiating crosslinking and generating localized microstructures with unprecedented precision. The development of magnetic microrobot control strategies will enable control of microrobotic swarms for large-scale delivery of PEG. Microrobots capable of triggered delivery of molecules at desired coordinates with high precision will also enable spatiotemporal control of bioactive molecules and factors which can be used to temporally alter cellular function. To confirm the survival, metabolic activity, and proliferative capacity of cells in/on these microrobotically patterned, cytocompatible bioelastomeric hydrogels, commercially available human mesenchymal stem cells (hMSCs) will be encapsulated in/on the patterned RLP-based hydrogels and their proliferation will be tested.The proposed research was submitted in response to the NSF2026 Idea Machine winning entry "Engineered Living Materials".This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.