CAREER: Genetically Programmable Protein Nanofibers for Mechanically Tunable Engineered Living Materials

NON-TECHNICAL SUMMARY: Traditional materials like steel, plastics, and polyester, have built the modern world. However, they are passive and cannot sense their surroundings or repair themselves. In nature, living materials like tree bark, skin, and coral reefs are never passive; they constantly sense the environment, repairing themselves and self-regenerating. The goal of this project is to develop a new class of materials, known as Engineered Living Materials (ELMs), that are produced by living microbial cells rather than manufactured through traditional energy-intensive chemical processes. ELMs are central to biotechnology applications because they combine the mechanical properties of man-made materials with the resilience and intelligence of living materials from Nature. The core of this research utilizes specific protein building blocks that are produced by bacteria and assemble into nanofiber networks. These networks can be used to make bioplastics and gels. Using rational design and Artificial Intelligence (AI), the proteins can be programmed at the genetic level to achieve mechanical properties of interest. The knowledge learned from this project will advance the ability to develop a roadmap for predicting how protein modifications assemble into larger structures with specific properties. To bridge the gap between the lab and society, this project will also promote public awareness of ELMs through accessible storytelling in blogs and podcasts, illustrating how biological technologies can build a more sustainable world. At the same time, it will empower K-12 students in rural regions by establishing a virtual mentoring network that connects them to active research and opens doors to future STEM careers. By training students across biology, materials science, and engineering, this project cultivates the next generation of a skilled workforce capable of leading the future of biomanufacturing and the U.S. bioeconomy. TECHNICAL SUMMARY: The emerging field of Engineered Living Materials (ELMs) seeks to develop life-like, intelligent materials that offer significant advancements in biotechnology. However, a critical barrier to current protein-based ELM applications is the inability to precisely control their mechanical behavior. This CAREER project addresses this challenge by establishing a fundamental framework for the design and predictive biosynthesis of ELMs with tunable mechanical properties. The research seeks to investigate the sequence–structure–property relationships of the beta-solenoid protein as programmable building blocks for ELMs. By employing rational design and AI-guided structure prediction methods, the project establishes a predictive roadmap that links protein sequence, structure, and material properties. Specifically, the research aims to: (1) determine how the radial and axial dimensions of beta-solenoid protein building blocks modulate the persistence length and stiffness of individual nanofibrils, (2) engineer flexible protein nanofibrils by incorporating disordered peptide motifs into the rigid core, and (3) generate macroscopic ELMs, such as bioplastics and hydrogels with user-defined mechanical performance to evaluate how nanoscale design parameters govern bulk mechanical behavior. By establishing predictive design principles across molecular, nanoscale, and macroscopic levels, this work advances fundamental understanding of protein-based materials and enables the development of genetically programmable systems with defined mechanical properties. The outcomes will advance fundamental understanding of biopolymer assembly and enable the development of genetically programmable materials for applications in biotechnology, medicine, and advanced manufacturing. To support the U.S. bioeconomy, the project integrates a multidisciplinary training and outreach plan to cultivate a skilled and diverse workforce. This includes developing research and training opportunities for undergraduate and graduate NSF Award ID: 2543391 | Program: 01003031DB NSF RESEARCH & RELATED ACTIVIT,01002627DB NSF RESEARCH & RELATED ACTIVIT,01002930DB NSF RESEARCH & RELATED ACTIVIT | Principal Investigator: Anna Duraj-Thatte | Institution: Virginia Polytechnic Institute and State University, BLACKSBURG, VA | Award Amount: $440,018 View on NSF Award Search: https://www.nsf.gov/awardsearch/show-award/?AWD_ID=2543391 View on Research.gov: https://www.research.gov/awardapi-service/v1/awards/2543391.html