Photostimulation of In Vitro Cardiac Tissue Models via Programmable Peptide Coassembly of Cell-Interfacing Donor-Acceptor Aggregates

PROJECT SUMMARY Natural biomacromolecular interactions utilize non-covalent interactions to generate stable, hierarchically ordered structures critical for their biological function. In this project, we develop a biomolecular-based technology to produce cell-internalizable nanostructures that can locally deliver photocurrents to cardiomyocytes. We aim to address the current limitations associated with bulky electrodes with low spatial resolution for stimulating excitable cells. We will use complementary peptide pairs to drive the sequence- controllable organization of energy transporting organic donor-acceptor units (quaterthiophene and perylene diimide) under physiologically relevant conditions. Molecular to microscale order is critical to the device efficiency of organic electronic materials, therefore highlighting the importance of the role of the self-assembling peptides. Peptides also make these systems water- processable and can include bioactive groups to be recognized by cells. The resulting free-standing nanostructures are designed to be photocurrent-generating and cell-interacting, and thus can be considered as phototransducer cardiac biomaterials. We desire that these peptides exhibit optoelectronic properties while mimicking cues that allow for the directed interactions of materials with cardiac cells. Moreover, the success of demonstrating the efficacy of these materials for cellular photostimulation can complement optogenetic techniques, but without relying on genetic modification techniques nor being limited by the target species. We hypothesize that photoinduced processes by the proposed peptidic coassemblies potentiate surface charging that is sequence/order tunable, leading to visible light cellular depolarization and stimulation of cardiomyocytes and cardiac tissues with high spatiotemporal resolution. To test this hypothesis, we will conduct the following Aims: (1) establish the conditions that allow for ordered coassembly formation and tissue contraction pacing by a model charge complementary donor-acceptor peptide pair with known photocurrent-generating capabilities; and (2) correlate structural order with photostimulation efficiency for a library of designer complementary linear and cyclic peptide pairs. These efforts are rationalized by the established transduction ability of analogous photovoltaic donor-acceptor polymer blends, previously shown to trigger action potential firing in other excitable cells. Our overarching goal is to achieve cell-interacting and photoexcitable peptidic nanostructures as cardiac biomaterials capable of influencing cellular behavior with high spatial resolution. Our vision is that this innovative technology will pave the way for a future where we can wirelessly control, monitor, repair, or regenerate native cells within the human myocardium in real time and in a targeted manner using tissue-penetrating light wavelengths.