DMREF/Collaborative Research: Computationally Driven Design of Synthetic Tissue-Like Multifunctional Materials

In nature, living cells join to form tissues capable of collective behaviors, such as sensing and responding to external cues, communicating, sorting and storing chemical species, and adapting their mechanical properties to sustain necessary loads. Biological tissues achieve these desirable properties because of careful control over the contents, arrangements, and interconnections of individual cells, an approach that yields hierarchical materials with high levels of adaptability, responsiveness, and tunable mechanical strength. Replicating these types of emergent properties in synthetic materials remains a major engineering challenge. This Designing Materials to Revolutionize and Engineer our Future (DMREF) award supports basic research and scientific development of material systems that mimic the composition, organization, and properties of living tissues. The computationally led designs of tissues-like materials with precise compositions and spatial arrangements seek to offer a generalizable solution for applications in artificial tissue replacement, wound healing, soft robotics, and embedded computing technologies. In addition, the project will support the technical and professional development of the STEM workforce by promoting the participation of high school, undergraduate, and graduate students, especially from the first-generation and underrepresented groups, through various outreach and research activities. This project aims to study synthetic tissues comprised of independent cell-like compartments coupled hierarchically through mechanical tethering (i.e., self-assembling block copolymer microgels (BCPs) as synthetic cytoskeleton) and selective transport (i.e., protein-enriched biomimetic membranes (BMs) as selective barriers) mechanisms and incorporating stimuli-responsiveness (e.g., via polymers and membrane proteins) into the compartments. Computational approaches combine molecular transport, stimuli-responsive coupled deformations of BCPs, intercompartment adhesion, and biomembrane mechanics to predict failure behaviors, emergent properties, and functionalities of tissue-like assemblies. An iterative feedback loop between theory, computations, synthesis of BCPs, 3D bioprinting, and microscale mechanical characterization is central to the project for validating predictions, informing model development, and creating a modular database. The construction of a compartmentalized material system that exhibits selective internal transport pathways via lipid- and protein-based BMs and tunable mechanical properties via BCPs will be achieved by understanding how the tunable hydrophobic and hydrophilic regions of BCPs: 1) interact with amphiphilic BMs at the nanoscale; 2) self-assemble and entangle to form solid-like gels at the microscale; 3) cross-link between compartments at the macroscale to rigidify the entire assembly. Ultimately, this project will provide the quantitative knowledge base and modular design criteria to accelerate the assembly and use of compartmentalized tissue-like materials that are multifunctional, stimuli-responsive, adaptable, tough, and operate outside of equilibrium. This project is co-funded by the Division of Civil, Mechanical and Manufacturing Innovation in the Directorate for Engineering and the Division of Materials Research in the Directorate for Mathematical and Physical Sciences. 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.