(6ao) Biologically Inspired, Electrically Active Membranes for Sustainability and Medicine

Like the metal- and semiconductor-based circuitry that has dominated the past century’s technological progress, biological systems also perform complex computation and fast electrical signaling over relatively long distances, but use the transport of ions in aqueous media instead of electrons to mediate signals. Bioelectricity is most impressively employed in specialized “excitable tissues” such as neurons, receptors, muscles, and the electric organs of fish such as the electric eel. The active component of each of these systems is a self-assembled nanoscale membrane containing exquisitely precise molecular machines that allow patches of membrane to toggle between functioning as resistors, capacitors, cables, or batteries in response to intracellular or extracellular stimuli. Excitable tissues are thus able to produce emergent electrical phenomena such as action potentials, defensive discharges, and signal integration while remaining soft, transparent, environmentally benign, and operating within biological constraints, unlike traditional electronics. In my program of research, I propose to use the design playbook of excitable tissues and the toolkit of responsive polymer chemistry to develop novel active material schemes that transduce and integrate signals and energy from environmental gradients and stimuli. My aim is to develop platform technologies that can be deployed in contexts that leverage the autonomously stimuli-responsive and biologically benign character of the materials involved, such as sustainable building materials, distributed sensors, and medical devices. My initial efforts will include three main projects:

(1) Active polymer membranes for novel ionotronic devices. Using soft materials such as hydrogels and dielectric elastomers, my group will engineer synthetic schemes inspired by various neuronal architectures that generate and integrate electrical signals from environmental stimuli. Building on my ongoing postdoctoral work on electrical responses from switchably permselective cross-linked polymer membranes as a sensing modality, I intend to develop ionotronic networks that incorporate signal multiplexing and feedback loops in order to engineer complex electrochemical responses (e.g. logic gating, oscillations) to environmental stimuli including light, chemical cues, and others. Possible applications range from implantable devices to consumer product packaging materials capable of autonomous homeostatic interventions.

(2) Engineering and electrophysiological study of lipid and block copolymer membranes. In addition to developing devices based around polymer membranes as described above, I intend to apply recent advances in engineering stable lipid bilayers and similar self-assembled membranes for use both in devices and in the fundamental study of the biophysics of membrane-bound molecular machines such as ion channels and transporters. In particular, I am interested in using electroconformational coupling to drive biochemical reactions and transport at the molecular level in the membrane environment in order to elucidate the mechanism of transporter-mediated disease states and to enable new functionality within biomolecular assemblies for use in medicine.

(3) Energy harvesting from unrecognized natural gradients. Between all manner of naturally-occurring aqueous solutions (e.g. rivers, oceans, xylem, phloem, blood, sweat, tears) there exist large concentration differences of sodium chloride, other electrolytes, and neutral osmotic drivers. While a body of literature has appeared around extracting usable electrical energy on the kilowatt scale by combining fresh and salt water through schemes such as reverse electrodialysis and pressure-retarded osmosis, less effort has been spent on seeking out untapped biological and/or environmental streams to exploit for smaller-scale power generation. My lab will seek to use existing gradients maintained by biological homeostatic mechanisms or natural fluid flows to implement power generation schemes for low-power electronics such as medical implants or distributed environmental sensors.

Research Experience:

The “biophysics-inspired materials engineering” research agenda that I intend to pursue is the culmination of a highly interdisciplinary set of research experiences and a curiosity and reverence for the way evolved systems accomplish tasks related to their survival.¹ After an undergraduate background in organic chemistry,² I joined Prof. Michael Mayer’s biophysics group at the University of Michigan while pursuing my Ph.D. in chemical engineering. My work there (and at the Adolphe Merkle Institute in Switzerland, where the group later moved) convinced me of the central importance of membranes as mediators of the flow of energy and matter in biological systems – and, accordingly, of their promise in engineered systems.

During my Ph.D., I first became interested in excitable tissues when my colleagues and I engineered an entirely hydrogel-based electrical power source capable of generating high voltages (>100 V) from salt gradients by replicating the functions of the main components of an electric eel’s specialized organs with a series of hydrated polymer analogues.³ We also designed a pressure generator for soft robotic actuation that relied on osmotic gradients across polymer membranes in a manner similar to the cells responsible for fast motion in plants.⁴ Additionally, we performed fundamental⁵ and applied⁶ studies of self-assembled membranes composed of synthetic bolaamphiphilic lipids of a type found in single-celled hyperthermoacidophiles, as well as electrophysiological studies of the voltage-driven assembly of engineered ion channels in lipid membranes.⁷

My postdoctoral research in Prof. Joanna Aizenberg’s bioinspired materials group at Harvard University has involved incorporating various stimuli-responsive chemistries into polymer membranes to induce switchable permeability and lateral signal transmission.

Teaching Interests:

I would be happy to teach thermodynamics and transport at an introductory or advanced level, as well as more specialized classes on polymer chemistry, self-assembly, bioconjugation techniques, biophysics, and nanomaterials. I would also be interested in giving classes or seminars on responsible research conduct and general research practices (e.g. keeping a notebook, using tools to review the literature, selecting a reference manager, and writing a journal article). Further, I am excited to teach and mentor students from diverse backgrounds.

I would like to create a classroom environment that leverages real-world examples and demonstrations whenever possible in order to teach the principles of science and engineering while providing real-world context. In particular, biology is teeming with compelling applications of physical principles that could make interesting case studies. Finally, I have found that some of my most interesting moments in the classroom have come from narrative explanations of how we humans have historically figured out the universe’s truths. For example, only after enabling developments in electrical engineering (the voltage clamp) and marine biology (the discovery of the squid giant axon) were Hodgkin and Huxley able to gather the data required to hypothesize that voltage-gated ion conductances were the mechanism behind the action potential, for which they won a Nobel prize. Following the luck and logic of our precursors helps us to demonstrate model-building and inference while motivating interdisciplinary work. In the classroom, I’ll make sure my students don’t lose sight of the giants on whose shoulders we stand.

Selected Publications:

(1) Schroeder, T. B. H.; Houghtaling, J.; Wilts, B. D.; Mayer, M. It’s Not a Bug, It’s a Feature: Functional Materials in Insects. Adv. Mater. 2018, 30, 1705322. https://doi.org/10.1002/adma.201705322.

(2) Dugal-Tessier, J.; O’Bryan, E. A.; Schroeder, T. B. H.; Cohen, D. T.; Scheidt, K. A. An N-Heterocyclic Carbene/Lewis Acid Strategy for the Stereoselective Synthesis of Spirooxindole Lactones. Angew. Chem. Int. Ed. 2012, 51 (20), 4963–4967. https://doi.org/10.1002/anie.201201643.

(3) Schroeder, T. B. H.; Guha, A.; Lamoureux, A.; VanRenterghem, G.; Sept, D.; Shtein, M.; Yang, J.; Mayer, M. An Electric-Eel-Inspired Soft Power Source from Stacked Hydrogels. Nature 2017, 552 (7684), 214–218. https://doi.org/10.1038/nature24670.

(4) Bruhn, B. R.; Schroeder, T. B. H.; Li, S.; Billeh, Y. N.; Wang, K. W.; Mayer, M. Osmosis-Based Pressure Generation: Dynamics and Application. PLoS ONE 2014, 9 (3), e91350. https://doi.org/10.1371/journal.pone.0091350.

(5) Schroeder, T. B. H.; Leriche, G.; Koyanagi, T.; Johnson, M. A.; Haengel, K. N.; Eggenberger, O. M.; Wang, C. L.; Kim, Y. H.; Diraviyam, K.; Sept, D.; et al. Effects of Lipid Tethering in Extremophile-Inspired Membranes on H+/OH− Flux at Room Temperature. Biophys. J. 2016, 110 (11), 2430–2440. https://doi.org/10.1016/j.bpj.2016.04.044.

(6) Eggenberger, O. M.; Leriche, G.; Koyanagi, T.; Ying, C.; Houghtaling, J.; Schroeder, T. B. H.; Yang, J.; Li, J.; Hall, A.; Mayer, M. Fluid Surface Coatings for Solid-State Nanopores: Comparison of Phospholipid Bilayers and Archaea-Inspired Lipid Monolayers. Nanotechnology 2019, 30 (32), 325504. https://doi.org/10.1088/1361-6528/ab19e6.

(7) Fennouri, A.; Mayer, S. F.; Schroeder, T. B. H.; Mayer, M. Single Channel Planar Lipid Bilayer Recordings of the Melittin Variant MelP5. Biochim. Biophys. Acta BBA - Biomembr. 2017, 1859 (10), 2051–2057. https://doi.org/10.1016/j.bbamem.2017.07.005.