Optical imaging has transformed our ability to visualise biological processes in living systems, yet many key biological features remain difficult to access: molecular identity deep inside scattering tissues, mechanical forces acting across cells and tissues and dynamic cellular states that require precise optical readouts. My laboratory develops optical probes and imaging strategies that convert these otherwise hidden biological properties into measurable signals in vivo.
In this talk, I will first introduce our work on biodegradable bioharmonophores: polymer-encapsulated, self-assembling peptide-based nonlinear probes that generate strong second-harmonic signals. These probes combine photostability, low-background nonlinear contrast, biodegradability and molecular targeting, enabling high-resolution in vivo detection of single cancer cells in zebrafish embryos. I will discuss how this concept could be extended toward deep-tissue imaging in highly scattering environments, including intact bone and bone marrow.
I will then highlight complementary efforts to engineer genetically encoded and optically controllable reporters, including GenEPi-based approaches for visualising mechanobiological activity and primed-conversion strategies for converting dynamic biological events into persistent optical marks. Together, these technologies aim to expand the optical toolbox from passive imaging toward functional, targeted and history-recording readouts of living systems.
More broadly, I will discuss how engineered optical reporters — synthetic, biodegradable, genetically encoded and photo-convertible — can help bridge nanomaterials, nonlinear microscopy and cell biology, opening new possibilities for studying biological dynamics across scales.
Key references
- Yaganoglu, S., Kalyviotis, K., et al. Highly specific and non-invasive imaging of Piezo1-dependent activity across scales using GenEPi. Nature Communications 14, 4352 (2023).
- Sonay, A. Y., Kalyviotis, K., Yaganoglu, S., Unsal, A., Konantz, M., Teulon, C., Lieberwirth, I., Sieber, S., Jiang, S., Behzadi, S., Crespy, D., Landfester, K., Roke, S., Lengerke, C., & Pantazis, P. Biodegradable Harmonophores for Targeted High-Resolution In Vivo Tumor Imaging. ACS Nano 15, 4144–4154 (2021).
- Dempsey, W. P., Georgieva, L., Helbling, P. M., Sonay, A. Y., Truong, T. V., Haffner, M., et al. In vivo single-cell labeling by confined primed conversion. Nature Methods 12, 645–648 (2015).
Keywords
Bioharmonophores; nonlinear microscopy; second-harmonic generation; biodegradable optical probes; GenEPi; mechanobiology; primed conversion; in vivo imaging; deep-tissue imaging.
