(6av) Engineering DNA-Polymer Assemblies

--Advisor: Carlos Castro, Mechanical and Aerospace Engineering, Ohio State University

Postdoctoral research: “Polyelectrolyte Complexation with Biomolecules”

--Supervisor: Matt Tirrell, Pritzker School of Molecular Engineering, University of Chicago

Research Interests:

Chemical and biological systems exist in a mechanical environment. Across multiple scales tissues, cells, proteins, nucleic acids, and other biomaterials generate and are subjected to mechanical signals such as force, stress, and flow. The way these signals affect function and movement is still largely unknown. Modern polymer and DNA nanotechnology provides materials to build custom nanoscale devices with unprecedented control over physical and chemical properties. I aim to engineer devices at the scale necessary to investigate the mechanical and chemical interactions between various biomolecules and their environment. Employing the specificity of DNA assembly and the tunability and robustness of polymer assemblies can help achieve these goals.

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. These joints and mechanisms were then used to demonstrate multiple actuation methods used to control the configuration of these nanostructures. A novel actuation method I developed allows for real-time control of DNA-based devices using a network of low affinity connections. This groundwork will enable the construction of complex engineering devices in the future.

My postdoctoral research uses polyelectrolytes and biomaterials as robust building blocks for self-assembled nanoparticles and customizable materials. This work uses charged homo- and block copolymers to complex therapeutic nucleic acids and proteins to develop particles and materials with programmable functionality. A thorough investigation of chemical structure - physical property relationships and their effect on stability of these particles and materials enables efficient design and construction of delivery devices for therapeutic payloads.

Future Research:

As an independent investigator my laboratory will focus on the design, assembly, and implementation of nanodevices made from biomaterials. Building on my experience in DNA nanotechnology and polymer science, I plan to explore the following directions:

1. Programmable DNA-Polymer Assemblies. Employing the vast geometric, mechanical, and chemical design space of DNA nanotechnology with robust functional polymer assemblies, I plan to engineer materials and nanoparticles with programmable features useful in measuring, sensing, and delivery. To achieve this goal the extensive design parameters will be utilized for global and local responsiveness to ion conditions, pH, temperature, or the presence of biomolecules. Additionally, static assemblies with structural DNA networks will permit specific placement and patterning of molecules like polymers, peptides, or antibodies to study specific interactions.
2. Functional Polyelectrolyte Complex Micelles (PCMs) for Delivery of Biomolecules. Self-assembling hydrophilic neutral-charged block copolymers with charged therapeutically relevant nucleic acids and proteins 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.
3. Multiscale Assembly and Actuation of DNA Mechanisms. Structural DNA nanotechnology allows engineers to design devices with unprecedented geometric precision. However, large assemblies of multiple DNA structures have poor reproducibility and little control over size and shape. I aim to optimize the macromolecular assembly of DNA nanostructures into micron-scale filaments and networks for materials and biomolecular applications. Further goals for this project include covalent and non-covalent addition of polymers to microscale DNA assemblies for stability purposes and programmable actuation of robotic microscale devices using non-traditional methods including motor proteins.

Teaching Interests:

I am interested in teaching Polymer Mechanics, Biomolecular Design, Systems/Controls, Dynamics, Thermodynamics, and Fluid Mechanics. I have two years of experience as a graduate teaching assistant in both large lecture and laboratory settings and I have taught numerous guest lectures.

Successful Proposals:

• NSF Nanomanufacturing (contributor)
• Presidential Fellowship, Ohio State University (lead)
• Molecular Foundry at Lawrence Berkeley National Lab (2) (lead)
• Advanced Photon Source at Argonne National Laboratory (lead)

Selected Publications (Chronological, of 14 total journal articles, Google Scholar h-index: 10):

• 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)
• 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)
• Lauback, S., Mattioli, K., Marras, A.E., Armstrong, M., Rudibaugh, T., Sooryakumar, R., Castro, C.E. “Real-time magnetic actuation of DNA nanodevices via modular integration with stiff micro-levers” Nature Communications. 9:1446(2018)
• 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)
• Marras, A.E., Zhou, L., Kolliopoulos, V., Su, H.J., Castro, C.E. “Directing folding pathways for multi-component DNA origami nanostructures with complex topology.” New Journal of Physics. 18:055005 (2016)
• 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)
  • Highlighted in Nature Materials, Nature Nanotechnology, PNAS
• 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)
• Zhou, L., Marras, A.E., Su, H.J., Castro, C.E. “DNA origami compliant nanostructures with tunable mechanical properties.” ACS Nano. 8:27-34 (2014)