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.

Grant Number: 1R21HL177481-01
NIH Institute/Center: NIH
Principal Investigator: Herdeline Ann Ardona