Genetically-Controlled Protein-Based Polymeric Materials Towards Mimicking Erythrocyte Mechanics

To reduce the toxicity and side effects of drugs, targeted intravenous delivery of drugs by nano/microparticles has been developed. Yet, the efficacy of the treatment is greatly reduced by biological organ filters that remove these delivery particles from the bloodstream, which then requires higher drug doses to ensure efficacy but increase adverse side effects. To date, research has mainly focused on geometric and electrostatic properties of delivery particles to improve their efficacy. Still, they lack the necessary mechanical properties to avoid filtering. Since erythrocytes pass through biological filters, the approach will be to mimic their mechanical behavior in protein polymer-network (PPN) materials. Discovered nanomechanics of specific protein tertiary structures are related to the mechanical properties of erythrocytes. However, it is still unclear how to incorporate these proteins into the PPN materials that can properly translate protein nanomechanics.<br/><br/>Here, we developed genetically-controlled protein polymers to identify design rules that will allow translation of protein nanomechanics to the micro/macroscale materials. In this protein polymer design, protein cross-linkers genetically fuse at the ends of protein polymer chains, containing protein tertiary structures. In buffer solutions, functionalized protein polymers bind to each other via self-recognition and noncovalent interactions and/or covalent bonds, and consequently form PPN materials, specifically hydrogels. By controlling the characteristics of protein polymer chains (i.e., composition, structure, and symmetry) and modulating crosslinker types as well as performing mechanical testing, we identified the specific design rules for the chain and the crosslinker that will properly exhibit protein nanomechanics at the micro/macroscopic material level. This design discovery will culminate in a protein polymer platform that harnesses mechanical proteins with diverse tertiary structures into biomimetic mechanical materials, which we expect to advance a wide variety of healthcare applications, including but not limited to erythrocyte-mimicking PPN-based microparticles that can pass through biological filters in the human body.