Designing and Understanding High-performance Titin Polymers Using Synthetic Biology

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Non-technical description:Synthetic biology offers a new route of material production from renewable feedstock (such as biomass-derived sugars) through environmentally-friendly processes. Furthermore, synthetic biology enables more precise control over material properties. This project will use synthetic biology to produce, characterize, and understand a new type of protein-based fiber material, called titin polymers, that will be produced from renewable feedstock using engineered bacteria. This project will provide currently unknown details about sequence-property relationships in titin polymers that can guide design of future high-performance biomaterials. This project will also create multiple novel polymers from diverse protein and organism sources that may have outstanding mechanical properties. Additionally, this project will serve as a critical proof-of-concept for using synthetic biology to not only produce biomaterials but also understand the molecular mechanisms of biomaterials. The proposed synthetic biology strategy can be used to study many other types of materials. This project will also benefit society by creating new high-performance biomaterials that can potentially replace synthetic fibers made from petroleum feedstock, thus reducing CO2 emission and protecting the environments.Technical description:The goal of this project is to use this synthetic biology strategy to design, synthesize, characterize, and analyze a new type of ultra-high molecular weight (UHMW) titin polymers to understand the relationship between protein sequences and material mechanical properties. This project will use synthetic biology approaches to synthesize a series of UHMW titin polymers with different but precisely controlled monomer (i.e., immunoglobulin (Ig) domain) compositions and orders and with mutations on either the surface or core residues of the Ig domains. These different UHMW titin polymers will be spun into fibers, and fiber mechanical properties will be characterized. By analyzing the mechanical properties of fibers made from different titin polymers, this project will uncover the sequence-property relationships that give rise to the high tensile strength, toughness, and damping energy of the titin fibers. Specific aims include (1) understanding the effect of Ig-Ig interactions on fiber strength and toughness, (2) understanding the effect of Ig folding energy on fiber damping energy, and (3) exploring diverse Ig domains from genome database for novel polymers. Knowledge learned from this project will translate into design rules to guide future engineering of microbially-produced high-performance titin fibers with predictable properties for a broad range of applications.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.