Biology subjects

Baghdasaryan, A.

Publications and source records attributed to Baghdasaryan, A..

4 recordsLinked to original sources

bioRxiv2026

Refractive index modulation by ultraviolet absorption of canonical amino acids for in vivo optical transparency

The inherent opacity of most mammalian tissues limits deep-tissue optical imaging and light delivery. In contrast, the natural transparency of certain species and ocular tissues has been hypothesized to involve proteins with unusually high refractive indices. Here, we systematically analyze the ultraviolet absorption and visible-range refractive index modulation of canonical amino acids to identify key contributors to high-refractive index proteins. We identify arginine as a leading candidate, combining strong ultraviolet absorption, efficient refractive index modulation, physiological pH, and biocompatibility. These properties are validated through successful achievement of optical transparency in both ex vivo and in vivo tissues. Our findings establish a foundation for using abundant endogenous biomolecules to achieve in vivo tissue transparency and suggest a strategy for engineering proteins enriched in high-performing amino acids to enable efficient, biocompatible tissue clearing.

biophysics↗

bioRxiv2026

Tartrazine clears live cells while preserving viability at high refractive indices and osmolality

Tissue-clearing techniques have transformed optical imaging of fixed specimens, yet their application to living systems remains limited by toxicity and removal of key tissue components. We recently demonstrated that absorbing molecules such as tartrazine can reversibly render live mouse skin transparent. Subsequently, it was reported that isotonic protein solutions can achieve ex vivo and in vivo cellular clearing. However, discrepancies remain regarding the optimal refractive index (RI) for live-cell clearing and the impact of elevated osmolality on cell viability. Here, using cultured mammalian cells, we systematically examine the dependence of optical contrast on medium RI and the effects of hyperosmolality. We find that, contrary to the recent report of an optimal RI of 1.36[~]1.37 for suspended cells, densely-packed adherent cells exhibit a monotonic decrease in phase contrast up to an RI of 1.41 with tartrazine. Moreover, even under highly hyperosmotic conditions ([~]1200 mOsm/kg), cultured cells exhibit minimal deformation and negligible loss of viability for up to 30 min in the clearing solution. These results demonstrate that tartrazine enables effective live-cell clearing at RI up to 1.41 while preserving viability under elevated osmolality, and motivate future studies to define optimal conditions for in vivo optical clearing. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=44 SRC="FIGDIR/small/717314v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@1ec9fbforg.highwire.dtl.DTLVardef@1ebe9e6org.highwire.dtl.DTLVardef@1492c3corg.highwire.dtl.DTLVardef@f75559_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2025

Color-neutral and reversible tissue transparency enables longitudinal deep-tissue imaging in live mice

Light scattering in biological tissue presents a significant challenge for deep in vivo imaging. Our previous work demonstrated the ability to achieve optical transparency in live mice using intensely absorbing dye molecules, which created transparency in the red spectrum while blocking shorter-wavelength photons. In this paper, we extend this capability to achieve optical transparency across the entire visible spectrum by employing molecules with strong absorption in the ultraviolet spectrum and sharp absorption edges that rapidly decline upon entering the visible spectrum. This new color-neutral and reversible tissue transparency method enables optical transparency for imaging commonly used fluorophores in the green and yellow spectra. Notably, this approach facilitates tissue transparency for structural and functional imaging of the live mouse brain labeled with yellow fluorescent protein and GCaMP through the scalp and skull. We show that this method enables longitudinal imaging of the same brain regions in awake mice over multiple days during development. Histological analyses of the skin and systemic toxicology studies indicate minimal acute or chronic damage to the skin or body using this approach. This color-neutral and reversible tissue transparency technique opens new opportunities for noninvasive deep-tissue optical imaging, enabling long-term visualization of cellular structures and dynamic activity with high spatiotemporal resolution and chronic tracking capabilities. Significance StatementTissue scattering represents a major barrier to deep tissue imaging in vivo. We recently showed that tissue can be rendered transparent in the red spectrum using intensely absorbing dye molecules. Here, we introduce a new, color-neutral and reversible tissue transparency approach. We demonstrate longitudinal structural and functional imaging in the deep tissue of awake mice.

bioengineering↗

bioRxiv2021

Non-Invasive Confocal Fluorescence Imaging of Mice Beyond 1700 nm Using Superconducting Nanowire Single-Photon Detectors

Light scattering by biological tissues sets a limit to the penetration depth of high-resolution optical microscopy imaging of live mammals in vivo. An effective approach to reduce light scattering and increase imaging depth is by extending the excitation and emission wavelengths to the > 1000 nm second near-infrared (NIR-II), also called the short-wavelength infrared (SWIR) window. Here, we developed biocompatible core-shell lead sulfide/cadmium sulfide (PbS/CdS) quantum dots emitting at ~1880 nm and superconducting nanowire single photon detectors (SNSPD) for single-photon detection up to 2000 nm, enabling one-photon fluorescence imaging window in the 1700-2000 nm (NIR-IIc) range. Confocal fluorescence imaging in NIR-IIc reached an imaging depth of ~ 800 m through intact mouse head, and enabled non-invasive imaging of inguinal lymph nodes (LNs) without any surgery. In vivo molecular imaging of high endothelial venules (HEVs) with diameter down to ~ 6.6 m in the lymph nodes was achieved, opening the possibility of non-invasive imaging of immune trafficking in lymph nodes at the single-cell/vessel level longitudinally.

biochemistry↗