(2jv) Multifunctional Engineered Living Materials from Bacteria

Artificial materials have always been central to technological advancements, especially in biomedicine where increasingly sophisticated engineered tissues, sensors, batteries, and processors are being developed to restore functionality and extend and improve human life. To address disorders with complex spatiotemporal phenotypes in the body, there is a demand for new materials with multiple functions that are capable of responding to these complex phenotypes. Engineered living materials (ELMs) are composites of living cells embedded in a biopolymer matrix, in which cells control the biological activities of the material, and the matrix defines its physical properties. By de novo engineering both components we can produce living materials with unique combinations of physical and biological functions that can deliver superior therapeutic performances against multifactorial medical disorders. For example, ELMs can be programmed to adhere to a target tissue, sense and report the physiology of a certain organ, and dynamically release specific molecules in parallel. Over the last two decades, synthetic biology allowed us to program cells with a broad spectrum of non-natural biological properties; however, we have lacked the tools and design rules to genetically encode a synthetic matrix that programs collective cell self-organization into macroscopic structures and controls the physical properties of the final material. As result, most ELMs are microscopic and must be processed into macroscopic materials. As result, a few examples of macroscopic ELMs have been created by genetically modifying existing matrices or genetically manipulating the mineralization of inorganic matrices. I created the first macroscopic de novo ELM, which grows from bacteria engineered to produce a synthetic matrix. To achieve this goal, I engineered Caulobacter crescentus to display self-interacting proteins by replacing the central crystallization domain of the native surface layer monomer with a structural domain made of elastin-like polypeptides. This protein was found to be partially secreted, forming a matrix able to hierarchically organize cells over four orders of magnitude, resulting in the growth of centimeter-scale living materials. Remarkably, by modifying the structural domains of the matrix proteins, I tuned the mechanical properties of de novo ELMs over a 25-fold range. This study lays the foundation for growing ELMs with defined physical and mechanical properties. The goal of my future research is to combine my expertise in cell and matrix engineering to engineer multifunctional living materials for biomedical applications. To enable the encoding of complex functions, I plan to engineer both components of ELMs: the cells and the protein-based matrix. I will refactor the de novo ELM systems into different bacterial hosts (Aim 1) and investigate the relationship between matrix protein structure and the rheological properties of ELMs (Aim 2). I will ultimately direct this effort toward the development of therapeutic ELMs (Aim 3). This approach will allow for multiple iterations of cell and matrix engineering to achieve living materials with specific functions. My work will bridge synthetic biology, protein engineering, and materials science.

Teaching Interests:

I am looking forward to teaching chemical engineering core courses such as thermodynamics, general chemistry, biochemistry, principles of genetic circuit engineering, protein engineering, metabolic engineering, chemistry of proteins and nucleic acids, bioinformatics, biomaterials, and polymer chemistry.

I am also interested in teaching elective classes focused on the transformative synergy between synthetic biology and other disciplines, such as material science, biomolecular engineering, and therapeutic development. I will welcome students from different academic concentrations into my classroom to highlight that the contributions to this field as well as its possibilities are multifaceted. In this way, my goal is to teach students the value of an interdisciplinary approach to engineering that they can adopt in their future research and career.

Keywords:

Materials

Bioengineering

Biomaterials

Biomedical Engineering

Bionanotechnology

Molecular, Cellular, & Tissue Engineering

Protein Engineering

Synthetic Biology