(4dk) Biopolymer Physics for Health and Sustainability

My research will address two grand challenges, antibiotic tolerance and plastic pollution, using a biophysical approach that bridges theory and experiment. Bacterial infections remain a pressing concern due to bacterial tolerance to antibiotics. While much has been determined biochemically about both our immune response to infection and antibiotic tolerance mechanisms, I hypothesize that biophysical factors play a key role. Biopolymers in mucus and bacterial biofilms interact in dynamic ways that can form a physical barrier to prevent infection and hinder antibiotic diffusion, respectively. My approach will combine polymer physics theory development and engineered biomaterials as simplified models of these complex biological fluids to determine crucial physical parameters that influence infection development and antibiotic tolerance. Careful control of biopolymer physical behavior will allow us to develop a greater understanding of biopolymer physics in their naturally existing state. In a second research direction, my lab will make use of this developed physical understanding to engineer sustainable materials made from biopolymers with the aim of being both recyclable and biodegradable. Initial research areas in my proposed research program include investigating mechanisms of mucus dispersal of bacteria to combat infection, developing biofilm mimetic materials for testing eradication strategies, and engineering recyclable keratin-based plastic for single-use packaging.

Research Experience:

Engineering fully recyclable plastics from biopolymer-based polyelectrolyte complexes, Pritzker School of Molecular Engineering, University of Chicago (advised by Matthew Tirrell)

My postdoctoral research has focused on engineering fully recyclable plastics from biopolymer-based polyelectrolyte complexes. Creating a recyclable material that is not derived from fossil fuels could curb the exponential growth of plastic waste, which is now more than 260 million tons annually in the US, and decrease our reliance on and environmental pollution of petrochemicals. I have engineered a plastics alternative that is instead made from alginate and chitosan, biopolymers derived from biowaste products seaweed and shellfish or insect skeletons, respectively. The charged moieties on these biopolymers were chemically modified to possess stronger electrostatic interactions, allowing for: 1) polyelectrolyte complexation into a solid, and 2) ionic bond formation between polymers that could be reversibly broken simply by adding salt. Recyclability of the material was confirmed by repeated cycles of removing and adding salt and water. Mechanical characterization of films formed by biopolymer-based polyelectrolyte complexes showed sufficient stiffness and ductility to suit single-use plastic applications like candy wrappers. This work presents a new strategy for creating sustainable plastics that are both biodegradable and fully recyclable without contributing further to carbon emissions. To support this work, I was awarded the Arnold O. Beckman Postdoctoral Fellowship in the Chemical Sciences.

Polymer physics driven design and understanding of biological materials, Department of Chemical Engineering, Stanford University (advised by Andrew J. Spakowitz and Sarah C. Heilshorn)

My dissertation research bridged theory and experiment to develop a new framework that connected molecular-level parameters to macroscopic behavior for dynamically associating polymer networks. Polymers with dynamic associations are crucial in many emerging technologies like biomaterials, wearable electronics, soft robotics, and actuators due to the range of mechanical behavior achieved through tuning association kinetics. However, engineering these polymers to precisely control their viscoelasticity for a given application can be a long, iterative process. Ideally, viscoelasticity of these supramolecular networks can be modeled to predict the desired polymer network design, but theoretical models that have good agreement with experimental rheological data through fitting face a crucial pitfall: the parameters are not directly experimentally relevant. My PhD work included the derivation of a purely analytical theory to fill that gap of incorporating experimentally controllable, molecular-level parameters and linking those to predictions of bulk rheological behavior (Cai et al, Phys Rev E 2020). To validate my theory, I synthesized hyaluronic acid-based hydrogels with pendant host and guest molecules that dynamically associate (Cai et al, ACS Cent Sci 2022). Using a microrheology technique I refined (Cai et al, Soft Matter 2021), I characterized the rheological behavior of this hydrogel system with different host and guest pairs that resulted in a range of viscoelasticity. Brachiation parameters were first aligned with a subset of the rheological data then varied proportionally with experimental parameter changes to predict the rheology of the new formulations (e.g. higher polymer concentration). The agreement between theoretical predictions and rheological data demonstrated the utility of my theory as a valuable tool in future design principles of dynamically associating polymer materials.

I also applied my knowledge of polymer physics to a number of biological fluids with clinical significance. First, I used microrheology to characterize patient respiratory secretions and show that enzymatic degradation was an effective strategy in clearing fluid buildup in lungs of patients with severe COVID-19 infections (Kratochvil*, Kaber*, Demirdjian*, Cai et al. JCI Insight 2022). In a separate project, I investigated the biophysical properties of lung mucus from patients with cystic fibrosis, where the pathogen Pseudomonas aeruginosa is often the cause of chronic infections because of its antibiotic tolerance. I showed that biopolymers in lung mucus like DNA and a filamentous bacteriophage that is secreted by Pseudomonas can interact electrostatically with positively charged antibiotics (Chen* and Cai* et al, Science Adv 2024). This electrostatic interaction is coupled with liquid crystalline structures formed by the bacteriophages to hinder antibiotic diffusion to Pseudomonas. Insight into this mechanism inspired current work on antimicrobial peptides that tune the electrostatics of lung mucus biopolymers to aid antibiotic diffusion and efficacy. Lastly, I developed an in vitro model of the intestinal mucus layer and probed changes to the rheological properties of intestinal mucus from parasitic worm infections (Cai* and Braunreuther* et al, APL Bioeng 2024). Intriguingly, the rheological properties of intestinal mucus when probed in situ on the epithelial cells compared to extracted mucus were drastically different, demonstrating the significance of this experimental model.

Teaching Interests:

I am passionate about educating the next generation of chemical engineers both in the classroom and laboratory. In the classroom, my teaching philosophy will center on conveying the relevance of learned concepts to future professional success by supplying relevant real-world examples. In my lab, I will tackle problems across a range of applications, from sustainable materials to biomedical engineering, using an approach grounded in fundamental physics, rheology, biomaterials science, and cell biology. Training my students to have a strong foundation with this approach will prepare them for much more than their specific thesis projects. Overall, I want to foster an inclusive and collaborative learning environment in the classroom rather than a competitive one. I greatly benefitted in the classroom and in research from the knowledge and help of my peers. My goal is to foster peer-to-peer learning, which I will achieve by giving students the opportunity to help each other, both during class discussions and via mentoring structures.

My training at the undergraduate and graduate levels in chemical engineering gives me a strong grasp of the chemical engineering curriculum. I am qualified to teach all undergraduate and graduate chemical engineering courses, including transport, fluid mechanics, kinetics, thermodynamics, mass and energy balances, and statistical mechanics. Given my fields of expertise, I am interested in developing elective courses covering polymer physics, rheology, and polymeric materials for biomedical engineering. In graduate school, I was a teaching assistant for Applied Mathematics for Chemical and Biological Engineers. As a postdoc at UChicago, I gave a series of guest lectures in polymer dynamics for the graduate course Polymer Physics.

Service:

I believe that including diverse perspectives and lived experiences enables the pursuit of more complex challenges, novel solutions, and broadly impactful research. I have and will continue to support the development of an inclusive scientific community for students and researchers of all backgrounds, identities, and perspectives through outreach, mentoring, and leadership. Beginning in college, I have participated in outreach efforts to increase female representation in STEM. I ran a program for the MIT Society of Women Engineers to engage middle school girls with fun science experiments and co-founded MIT Code It!—a multi-day workshop that aims to jumpstart interest for coding in girls. I have mentored 4 undergraduate students and 4 high school students in scientific research. Two of my students were Stanford Undergraduate Research Fellows and first generation in their families to attend college, and later on I helped one of them with her graduate school applications. My high school student mentees were part of Stanford’s Future Advancers of Science and Technology program, which aims to teach high school students in low-income neighborhoods of San Jose how to conduct original scientific research across a range of topics. My mentees worked on projects ranging from building a trash-eating robot to studying quantum computing, and one is now attending MIT. I also served as the Vice President of the Chemical Engineering Graduate Student Action Committee at Stanford. In this position, I advised our department chair on the selection criteria for departmental fellowships and awards as well as helped to select student speakers for departmental convocation, advocating for more diverse representation. My ongoing mentoring and outreach efforts include being a mentor for UChicago’s Girls Advancing in STEM (GAINS) to expand the exposure of high school girls and non-binary students to STEM opportunities.