(4br) Biohybrid Responsive Materials for Cell-like Behavior

Biomolecular machinery communicates with chemical and physical signals to perform essential tasks in our cells. As engineers, we strive to mimic such functionality in a synergistic effort to both improve our understanding of nature and build our own tools using synthetic biomaterials. Polymer science and DNA nanotechnology enable us to build custom nanodevices and materials with unprecedented control over physical and chemical properties, exhibiting fundamental functionality we find in nature. My goal as an independent investigator is to develop nanodevices and emergent materials inspired by biology and macroscale engineering for programmed sensing, delivery, and actuation.

My lab will focus on two major research themes:

RNA delivery using tailored Polyelectrolyte Complex Micelles (PCMs). Self-assembling hydrophilic neutral-charged block copolymers with charged therapeutically relevant nucleic acids is a growing, promising area of research. Following extensive development and characterization of simple polymer-based systems, I plan to build tailored delivery devices with their application in mind. Focusing on how delivery vehicles behave and release cargo in serum, cells, and eventually animals, is the crucial next stage for therapeutic PCMs. This includes design for peptide-driven and pH-triggered endosomal escape, programmed disassembly and cargo release, and the addition of targeting peptides or ligands on the micelle corona.

Stimuli responsive, reconfigurable materials for cell-like behavior. Employing the vast geometric, mechanical, and chemical design space of DNA nanotechnology, I plan to engineer nanoparticles for molecular-level measurements of force, ionic conditions, pH, and the presence of biomolecules. Separately, we will create smart soft materials using polymer networks exhibiting programmable dynamic behavior by incorporating structural DNA filaments. In additional to controllable material properties, these networks will permit specific placement and patterning of molecules to study combinatory interactions. Ultimately, we will incorporate our previously described nanosensors into these networks for smart materials exhibiting molecular-level detection and macro-scale actuation response towards the dream of artificial cellular machinery.

Research Experience

Postdoc with Prof. Matthew Tirrell at University of Chicago, Molecular Engineering

My current research studies self-assembled nanoparticles and microscale materials containing charged polymers and nucleic acids. Focusing on the molecular details of each component, we develop structural-property relationships, finding drastic impact of molecular details (DNA vs RNA, as an example). Our findings have enabled us to design tailored micelles with therapeutic cargo to trigger immune response in cells and mice.

Consulting for SiO2 Materials Science

During the pandemic, I designed and created RNA containing lipid nanoparticles modeled off of the Moderna COVID-19 vaccine. I tested the nanoparticles’ size distribution and RNA encapsulation efficiency over time in the presence of six coatings for vials and syringes that SiO2 supplies to Moderna, and compared them to silicone oil (standard syringe lubricant), all at three temperatures. I found little change between coatings, but a faster deterioration under the presence of silicone oil and at higher temperatures.

PhD with Prof. Carlos Castro at Ohio State University, Mechanical Engineering

My graduate research expanded DNA origami technology by producing dynamic devices with programmable motion, an underpinning for my future research program. I developed nanoscale kinematic joints including hinges and sliders demonstrating rotational and linear motion. Borrowing concepts from macro-scale machine design, I used these fundamental components to build higher order mechanisms with specific 2D and 3D motion. Finally, we used these to demonstrate multiple actuation methods used to control mechanism configuration in near real-time. This groundwork will enable the construction of complex engineering devices in the future.

Teaching Interests

With my multifaceted academic background in polymer science, biophysics, and mechanical engineering, I am prepared to teach a range of engineering courses. My ideal course is an upper-level Biomolecular Systems course covering cell mechanics, self-assembly, and dynamics in biological systems. I hope to integrate a lab portion to expose students to common research tools used in related areas, allowing undergraduate and graduate students to experience interdisciplinary applications of engineering fundamentals. My classroom and laboratory will promote a continuously evolving learning environment that is inclusive, supportive, and stimulating.

Teaching Experience

I have 2.5 years of experience as a TA for Finite Element Method (FEM), Systems Dynamics, Mechanical Measurements, and Technical Writing. Additionally, I have taught numerous guest lectures in 7 different classes. My most fulfilling teaching experience is mentoring. I have mentored 11 students and 3 BIOMOD (undergraduate molecular design) teams. My mentees are from 5 different majors and many have gone on to win awards and prestigious scholarships and are now pursuing scientific careers at high levels. It has been incredibly gratifying to follow their careers and to learn as much from them as they learned from me.

Successful Proposals

• NSF CMMI, Nanomanufacturing - 2016 (contributor)
• Presidential Fellowship, Ohio State University - 2016
• Molecular Foundry at Lawrence Berkeley National Lab - 2017, 2018
• Advanced Photon Source at Argonne National Laboratory - 2018, 2019, 2020
• Spallation Neutron Source at Oak Ridge National Laboratory - 2020
• Stanford Synchrotron Radiation Lightsource at SLAC National Accelerator Laboratory - 2019
• Travel Award, Biophysical Society - 2017
• Ray Travel Award, OSU - 2015, 2017

Selected Publications (19 total, 7 first author)

Marras, A.E., Campagna, T.C., Vieregg, J.R., Tirrell, M.V., “Physical property scaling relationships for polyelectrolyte complex micelles” Macromolecules. (2021)

Marras, A.E., Zhou, L., Su, H.J., Castro, C.E. “Programmable motion of DNA origami mechanisms.” Proceedings of the National Academy of Sciences. 112:713-8 (2015)

Marras, A.E., Shi, Z., Lindell, M., Patton, R.A., Huang, C.M., Zhou, L., Su, H-J., Arya, G., Castro, C.E. “Cation-activated avidity for rapid reconfiguration of DNA nanodevices” ACS Nano. 12:9484-9494 (2018)

Fares, H.M., Marras, A.E., Ting, J.M., Tirrell, M.V., Keating, C.D., “Impact of wet-dry cycling on the phase behavior and compartmentalization properties of complex coacervates” Nature Communications. 11:5423 (2020)

Marras, A.E., Ting, J.M., Stevens, K.C., Tirrell, M.V., “Advances in the structural design of polyelectrolyte complex micelles” Journal of Physical Chemistry B. (2021)

Marras, A.E., Vieregg, J.R., Ting, J.M., Rubien, J.D., Tirrell, M.V. “Polyelectrolyte complexation of oligonucleotides by charged hydrophobic – neutral hydrophilic block copolymers” Polymers. 11:83 (2019)

Lei, D., Marras, A.E., Liu, J., Huang, C.M., Zhou, L., Castro, C.E., Su, H.J., Ren, G. “Three-dimensional structural dynamics of DNA origami Bennett linkages using individual-particle electron tomography” Nature Communications. 9:592 (2018)

Zhou, L., Marras, A.E., Su, H.J., Castro, C.E. “Direct design of an energy landscape with bistable DNA origami mechanisms.” Nano Letters. 15:1815-21 (2015)