Engineering Protein-based Multifunctional Biomaterials Using Molecular Simulations

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Predictive tools are crucial to accelerate material design for biomedical applications. Molecular simulations can provide atomic-resolution information on the fundamental properties of materials, bettering our understanding of the structure - function relationships and reducing the need for experimental trial and error. This research program focusses on engineering multifunctional protein-based biomaterials with a bottom-up approach, using large scale atomistic simulations and multiscale modeling. Protein-based biomaterials are biocompatible and biodegradable alternatives to their synthetic counterparts. They can be precisely engineered to display conformational properties such as folding upon binding, respond to environmental stimuli, and self-assemble. Their versatility and biocompatibility make them well-suited for a wide range of biomedical applications including drug and gene delivery. The long-term objective of this research program is to engineer protein and peptide-based, multifunctional gene delivery systems. We will harness the power of molecular simulations to provide a systematic approach to rational biomaterial design. Collaborations with experimental groups will be established to test the efficacy of the lead delivery systems in vitro and in vivo. In the short term, studies will be conducted to: (i) engineer biocompatible and biodegradable protein-based nanocages as siRNA delivery systems; (ii) design peptide fusion gene delivery systems capable of escaping endosomes; (iii) elucidate the dynamics of ligand-receptor interactions to better design active targeting strategies. The proposed studies will establish a framework for the use of computational techniques in biomaterial design and help develop non-toxic, targeted gene delivery systems. On a more fundamental level, the methodological insights gained from studying proteins and peptides as biomaterials will provide rigorous design strategies and predictive tools in the development of gene delivery systems. The research outcomes will help Canadian biomedical sector to engineer next generation biomaterials for cancer treatment.