# Optically Promoting Cardiac Maturation Using Engineered Peptides

> **NIH NIH R56** · UNIVERSITY OF CALIFORNIA-IRVINE · 2022 · $494,946

## Abstract

PROJECT SUMMARY
 The promise of human stem cell-derived cardiomyocytes (hSC-CMs) opens doors towards the
feasibility of personalized medicine against cardiac diseases and for performing more accurate drug
discovery studies. Moreover, hSC-CMs overcome the issue of species differences when using animal
models for high throughput screening studies. However, one of the bottlenecks for scaling up the use of
hSC-CMs is their ability to accurately reflect the native structure and function of adult human
cardiomyocytes. Current efforts to address this critical challenge involve maturation protocols that use
biophysical cues such as electrical and mechanical stimulation. These methods often utilize electrode
contacts for field stimulation, bulky instrumentation for mechanical or sustained chemical stimulation, or
genetically modifying cells to be light-responsive. Although we have seen successes through these
induction and stimulation approaches, the field would benefit from a stimulation approach with minimal
culture contact to reduce risk of infection during long-term cultures, as well as a light-based approach
with higher spatiotemporal resolution than electrode-based stimulation. Here, we propose a new
paradigm for stimulating hSC-CMs towards maturation by interfacing these cells with peptide-based
substrates that are engineered to convert light to electrical cues. Our team will develop peptides
engineered with chromophore units and cell-binding epitopes as materials that can be used for
photoelectrical conditioning of hSC-CMs towards maturation. The long-term goal of this project is to
establish photoelectrical conditioning via engineered peptides as a viable method to electrically stimulate
cardiomyocytes and promote hSC-CM maturation in an electrodeless and non-genetic manner, with
higher spatiotemporal resolution than field stimulation. We hypothesize that transient charging and other
associated light-induced processes at the cardiomyocyte-biomaterial interface can influence extracellular
potential, resulting in the photoelectrical stimulation of hSC-CMs towards maturation. Our rationale for
proposing a materials-based approach for stimulating hSC-CMs stems from previous reports of
conjugated polymers being used as a photoactive substrate for triggering action potentials of other
excitable cells. To test our hypothesis, we propose the following specific aims: (1) establishing design
parameters for peptide nanoassemblies with optimal photostimulation efficiency; (2) test the cellular- and
tissue-level impact of peptide-mediated photostimulation; and (3) elucidate the effect of the proposed
photoelectrical conditioning method on hSC-CM maturation. By establishing the design rules for the
proposed photoexcitable peptides for stimulating hSC-CMs and ensuring their capability to locally excite
cardiac cells, this innovative approach offers a new strategy for a “wireless” stimulation of cardiac tissues
and can significantly contribute towards addressing...

## Key facts

- **NIH application ID:** 10683790
- **Project number:** 1R56HL164348-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Herdeline Ann Mallari Ardona
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $494,946
- **Award type:** 1
- **Project period:** 2022-09-12 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10683790

## Citation

> US National Institutes of Health, RePORTER application 10683790, Optically Promoting Cardiac Maturation Using Engineered Peptides (1R56HL164348-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10683790. Licensed CC0.

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