This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2) NON-TECHNICAL SUMMARY: Millions of patients are treated with intravenous drug injections every year. To ensure efficacy without using drug injections with unnecessarily large amounts that can lead to adverse side effects, nano-/micro-particles has been developed. These particles deliver the drugs from intravenous solutions to a targeted disease location for effective administration with small drug amounts. Yet, the efficacy of the treatment is greatly reduced by biological organ filters, such as kidney or liver, that remove these delivery particles from the bloodstream. To overcome filtering, higher drug doses are still required to ensure efficacy, which again increases adverse side effects. The current particles do not possess mechanical properties to avoid filtering in the bloodstream. However, natural biological particles, such as red blood cells, are known to exhibit the proper mechanical properties to pass through organ filters. Based on this observation, this CAREER project proposes the breakthrough development of drug delivery microparticles based on protein polymers that will mimic the mechanical behavior of materials constituents of natural biological particles. This project combines the fields of materials science and engineering, synthetic biology, and multiscale mechanics to build the foundation of a new science for effective biomimetic microparticles in drug delivery systems. This project also implements the inclusive educational ecosystem and curricular transformations, and offers transdisciplinary research experiences to prepare and train a diverse cohort of students that will form the future U.S. workforce in the integration of materials science and engineering and protein polymer science. TECHNICAL SUMMARY: In current non-biological particle-based drug delivery modalities, up to 90% of the particles are removed by the body?s filtering organs; thus, reducing the efficacy of intravenous treatments of diseases. In contrast, natural biological particles, such as erythrocytes, are immune to organ filtering. Non-biological and biological particles differ in their mechanical behavior, a key property to avoid filtering. The objective of this CAREER project is to design, synthesize and characterize protein-based materials, composed of crosslinked protein copolymers, with tailored mechanical properties that mimic those of constitutive materials of natural biological particles. The research approach combines the revolutionary tools of synthetic biology (the ability of harnessing the power of genetic engineering to fabricate artificially engineered protein copolymers), of materials science and engineering (MSE) and of molecular to macroscale mechanics. With these tools, this research will (1) establish the scientific principles that determine the topology of synthetic protein copolymers with exceptional mechanical properties, (2) investigate the effects of protein copolymer topology on the formation, structure, and bulk mechanical properties of protein-based materials and (3) examine the morphology and in-fluid transport properties of protein-based erythrocyte-mimetic microparticles. This project fills a knowledge gap in biopolymer-network materials regarding multiscale relationships between structures of constitutive mechanical protein copolymers and mechanical response under externally applied forces with an emphasis on reversible stretchability and fatigue resistance. To train the next generation of biopolymer materials scientists and engineers, this project will revolutionize the teaching of biopolymer science in MSE by including design and processing principles of nonconventional materials from biopolymers and synthetic biology in a MSE curriculum and by implementing inclusive student research experiences. 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.