Gnann C., Sigaeva A., Le T., Cesnik A., Sariyar S., Mahdessian D., Schutten R., Raghavan P., Leonetti M. D., Lindskog C., Uhlén M., Axelsson U., Lundberg E. Dissecting autonomous enzymatic variability in single cells // 2026, accepted in Nature Communications, pre-print available at bioRxiv, DOI: 10.1101/2024.10.03.616530
Our proteome-scale screening shows that almost 40% of human metabolic enzymes are differentially expressed in the neighbouring cells with the same genetic background and environment, both in cell culture and tissues. A number of enzymes change not only the expression level, but also the subcellular distribution, possibly participating in multiple different cellular functions. This study highlights the need for spatial profiling of metabolic enzymes, using multiplexed and multimodal approaches to determine the correlations between enzyme expression, activity, and metabolic outcomes on single-cell and cell population levels.

Sigaeva A., Hutchings C., Cesnik A., Lilley K. S., Lundberg E. Subcellular localisation as a driver of protein function // Nature Reviews Molecular Cell Biology, 2026, 1-18, DOI: 10.1038/s41580-026-00947-3
In this review paper, we highlight the importance of the protein's molecular environment for its function. Molecular interactions necessary for correct function often happen only at the specific subcellular sites, and change in protein localisation can trigger a dramatic change in protein function. This is a highly dynamic and poorly understood process, which calls for implementing new detection, analysis and data integration techniques, as well as expanding the range of biological models in the field of spatial proteomics.

Nourreddine S., Doctor Y., Dailamy A., Forget A., Lee Y.-H., Chinn B., Khaliq H., Polacco B., Muralidharan M., Pan E., Zhang Y., Sigaeva A., Hansen J. N., Gao J., Parker J. A., Obernier K., Clark T., Chen J. Y., Metallo C., Lundberg E., Ideker T., Krogan N., Mali P. A perturbation cell atlas of human induced pluripotent stem cells // 2026, pre-print available at bioRxiv, DOI: 10.1101/2024.11.03.621734

Sigaeva A., Zijlema E., Zhang Y., Schirhagl R. Evolution of intracellular free radical load in colon adenocarcinoma cells over the course of butyrate-induced redifferentiation // 2026, pre-print available at bioRxiv, DOI: 10.1101/2023.03.22.533138

Zhang Y., Sigaeva A., Elias-Llumbet A., Fan S., Woudstra W., de Boer R., Escobar E., Reyes-San-Martin C., Kisabacak R., Oosterhuis D., Gorter A. R., Coenen B., Perona Martinez F. P., van den Bogaart G., Olinga P., Schirhagl R. Free radical detection in precision-cut mouse liver slices with diamond-based quantum sensing // Proceedings of the National Academy of Sciences, 2024, 121, 43, DOI: 10.1073/pnas.2317921121
In this proof-of-concept study we use quantum sensing to track the changes in free radical production in live liver slices exposed to a prooxidant or antioxidant. This is the first study demonstrating the potential for nanodiamond-based quantum sensing in live tissue biopsies.

Zhang Y.*, Sigaeva A.*, Norouzi N., Heijink H. I., Slebos D. J., Pouwels S. D., Schirhagl R. Dynamics for high-sensitivity detection of free radicals in primary bronchial epithelial cells upon cigarette smoke extract // Nano Letters, 2024, 24, 31, 9650-9657, DOI: 10.1021/acs.nanolett.4c02409

Sigaeva A., Li R., van Laar J., Wierenga L., Schirhagl R. Timing and mechanism of nanodiamond uptake in colon cancer cells // Nanotechnology, 2024, 17, 147-166, DOI: 10.2147/NSA.S464075

Li R., Vedelaar T., Sigaeva A., Zhang Y., Wu K., Wang H., Wu X., Olinga P., Wlodarzyk-Biegun M., Schirhagl R. Fluorescent Nanodiamonds for Tracking Single Polymer Particles in Cells and Tissues // Analytical Chemistry, 2023, 95, 35, 13046-13054, DOI: 10.1021/acs.analchem.3c01452

Pouwels S. D., Sigaeva A., de Boer S., Eichhorn I. A., Koll L., Kuipers J., Schirhagl R., Heijink I. H., Burgess J. K., Slebos D.-J. Host-device interactions: exposure of lung epithelial cells and fibroblasts to nickel, titanium, or nitinol affect proliferation, reactive oxygen species production, and cellular signalling // Journal of Materials Science: Materials in Medicine, 2023, 34, 38 DOI : 10.1007/s10856-023-06742-2

Sigaeva A., Merz V., Sharmin R., Hemelaar S. R., Schirhagl R., Krueger A. Intracellular behavior of nanodiamonds functionalised with a zwitterionic shielding moiety // Journal of Materials Chemistry C, 2023, 11, 6642-6650 DOI: DOI: 10.1039/D3TC00590A

Reyes-San Martin C., Zhang Y., Hamoh T., Berendse L., Klijn C., Li R., Sigaeva A., Kawałko J., Li H. T., Tehrani J., Mzyk A., Schirhagl R. Fluorescent nanodiamond labels: Size and concentration matters for sperm cell viability // Materials Today Bio, 2023, 20, 100629 DOI : 10.1016/j.mtbio.2023.100629

Wu K., Nie L., Nusantara A., Woudstra W., Vedelaar T., Sigaeva A., Schirhagl R. Diamond relaxometry as a tool to investigate the free radical dialogue between macrophages and bacteria // ACS Nano, 2023, 17(2), 1100-1111 DOI: 10.1021/acsnano.2c08190

Morita A., Nusantara A. C., Mzyk A., Perona Martinez F. P., Hamoh T., Damle V. G., van der Laan K. J., Sigaeva A., Vedelaar T., Chang M., Chipaux M., Schirhagl R. Detecting the metabolism of individual yeast mutant strain cells when aged, stressed or treated with antioxidants with diamond magnetometry // Nano Today, 2023, 48, 101704 DOI : 10.1016/j.nantod.2022.101704

Mzyk A.*, Sigaeva A.*, Schirhagl R. Relaxometry with Nitrogen Vacancy (NV) centres in Diamond // Accounts of Chemical Research, 2022, 55, 24, 3572-3580 DOI: 10.1016/j.nantod.2022.101704

Sigaeva A., Norouzi N., Schirhagl R. Intracellular Relaxometry, Challenges, and Future Directions // ACS Central Science, 2022, 8(11), 1484-1489 DOI: 10.1021/acscentsci.2c00976

Sigaeva A., Hochstetter A., Bouyim S., Chipaux M., Schirhagl R. Single-particle tracking and trajectory analysis of fluorescent nanodiamonds in cell-free environment and live cells // Small, 2022, 18(39), 2201395 DOI: 10.1002/smll.202201395Digital Object Identifier (DOI)
While quantum sensors can offer low detection thresholds, high selectivity and nanometer spatial resolution, the measurements in live cells often lack context, such as subcellular localisation and molecular environment of the sensor. We combined free radical sensing with nanorheological measurements to get an insight into the mechanical properties of the immediate surroundings of the nanosensor moving inside a cell. We were able to map free radical concentrations in 3D and detect the particle transition between cell compartments.

Sigaeva A., Perona Martinez F., Nusantara A. C., Mougios N., Chipaux M., Schirhagl R. Diamond based nanoMRI for quantum sensing of free radical production in cells // Small, 2022, 18(44), 2105750 DOI: 10.1002/smll.202105750
This is the first study mechanistically demonstrating the response of quantum nanoparticle sensors to the changes in the free radical production inside and in the vicinity of live cells. We used macrophages as a model system and detected the drop in free radical concentration after inhibiting nitric oxide synthase. It has been challenging to perform such measurements in real time, at single-cell and subcellular levels, recording both an increase and a decrease in free radical concentration with classical fluorogenic probes used in the field.

Reyes-San-Martin C., Zhang Y., Hamoh T., Berendse L., Klijn C., Li R., Sigaeva A., Kawalko J., Mzyk A., Schirhagl R. Nanoscale MRI for Selective Labelling and Localized Free Radical Measurements in the Acrosomes of Single Sperm Cells // ACS Nano, 2022, 16(7), 10701-10710 DOI: 10.1021/acsnano.2c02511

Sharmin R., Hamoh T., Sigaeva A., Mzyk A., Damle V. G., Morita A., Vedelaar T., Schirhagl R. Fluorescence nano-diamonds for detecting free radical generation in real time during shear stress in human umbilical vein endothelial cells // ACS Sensors, 2021, 6(12), 4349-4359 DOI: 10.1021/acssensors.1c01582

Zhang Y., Sharmin R., Sigaeva A., Klijn C. W. M., Mzyk A., Schirhagl R. Not all cells are created equal - endosomal escape in fluorescent nanodiamonds in different cells // Nanoscale, 2021, 13, 13294-13300 DOI: 10.1039/D1NR02503A

Morita A., Hamoh T., Sigaeva A., Norouzi N., Nagl A., van der Laan K. J., Evans E. P. P., Schirhagl R. Targeting Nanodiamonds to the Nucleus in Yeast Cells // Nanomaterials, 2020, 10(10), 1962. DOI:10.3390/nano10101962

Morita A., Hamoh T., Perona Martinex F. P., Chipaux M., Sigaeva A., Mignon C., van der Laan K. J., Hochstetter A., Schirhagl R. The Fate of Lipid-Coated and Uncoated Fluorescent Nanodiamonds during Cell Division in Yeast // Nanomaterials, 2020, 10(3), 516. DOI: 10.3390/nano10030516

Sigaeva A., Morita A., Hemelaar S. R., Schirhagl R. Nanodiamond uptake in colon cancer cells: the influence of direction and trypsin-EDTA treatment // Nanoscale, 2019, 11, 17357-17367. DOI: 10.1039/C9NR04228H

Sigaeva A., Ong Y., Damle V. G., Morita A., van der Laan K. J., Schirhagl R. Optical Detection of Intracellular Quantities Using Nanoscale Technologies // ACS Accounts of Chemical Research, 2019, 52, 7, 1739-1749. DOI: 10.1021/acs.accounts.9b00102

Van der Laan K. J., Naulleau J., Damle V. G., Sigaeva A., Jamot N., Perona-Martinez F. P., Chipaux M., Schirhagl R. Toward Using Fluorescent Nanodiamonds To Study Chronological Aging in Saccharomyces cerevisiae // ACS Analytical Chemistry, 2018, 90, 22, 13506-13513. DOI: 10.1021/acs.analchem.8b03431

Sigaeva A. O., Seriozhnikova N. B., Pogodina L. S., Trofimova N. N., Gur'eva T. S., Zak P. P. Changes of the choroid of different age groups of Japanese quails Coturnix japonica depending on the spectrum composition of illumination // Sensornye sistemy, 2015, v. 29, №4. p. 354-361.

Ignatov M. S., Ignatova E. A., Belousova A. A., Sigaeva A. O. Additional observations on protonemata of Schistostega pennata (Bryophyta) // Arctoa, 2012, 21, 1-20