CAREER: Programmable cellular remodeling of anisotropic hydrogels

Non-technical Abstract: Cell arrangements in nature have inherent directionality, from those lining the inside of the blood vessels, the striated muscle cells, to cardiomyocytes that power our beating hearts. These arrangements enable collective force generation across thousands of cells. Recreating these structures in the laboratory, however, remains challenging, and even when achieved, they often fail to function as expected. This is because processes such as cell movement, growth, and force generation are closely interconnected and difficult to control simultaneously. This project supports the development of complex, well-organized multicellular structures with fine-tuned interactions, drawing on concepts from liquid crystal physics. The project advances biotechnology by understanding how to design scaffolds to guide proper cell organization and force generation. The proposed work provides a reliable and cost-effective way to fabricate and evaluate scaffolds, with applications ranging from wound dressings and hygiene products to tissue regeneration and disease modeling. In addition, the project will foster interests in biomaterials and soft matter through integrated education, training, and outreach efforts, including K-12 outreach workshops, college research internships, curriculum development, and regional conferences for early-career scientists. Technical Abstract: Many tissues are intrinsically anisotropic, with this anisotropy dynamically maintained through cell division, migration, and steric interactions. Elongated cells can organize into structures resembling liquid crystals, following boundary cues, forming locally oriented domains, and generating topological defects. These emergent behaviors can be leveraged to create self-organizing, dynamic, cell-laden structures with orientational order across length and force scales spanning thousands of cells, mimicking highly anisotropic architectures observed in vivo. Local deformations generated by individual cells amplify anisotropic cues, drive long-range self-organization, and establish oriented force fields that guide morphogenic pathways. This project combines advanced characterization tools and material platforms inspired by liquid crystal physics to investigate how matrix properties influence collective cell alignment, how cell division and reorientation evolve over time to improve the quality of aligned structures, and how pre-patterned cell sheets drives programmed shape changes. These shape changes are reminiscent of those observed from liquid crystal elastomers, but are enriched by the interplay of cell activity and matrix remodeling at the macroscale. The overarching goal is to establish design principles for programmable cell dynamics by iteratively refining material systems, analyzing cellular responses, and developing predictive models. This capability to dictate cell orientation offers broad biotechnological potential, opening new paths towards tissue engineering, regenerative medicine, and the design of functional 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. NSF Award ID: 2541038 | Program: 01002627DB NSF RESEARCH & RELATED ACTIVIT,01002930DB NSF RESEARCH & RELATED ACTIVIT,01003031DB NSF RESEARCH & RELATED ACTIVIT | Principal Investigator: Yimin Luo | Institution: Yale University, NEW HAVEN, CT | Award Amount: $369,358 View on NSF Award Search: https://www.nsf.gov/awardsearch/show-award/?AWD_ID=2541038 View on Research.gov: https://www.research.gov/awardapi-service/v1/awards/2541038.html