Genes & CellsGenes & CellsГены и КлеткиGenes and Cells2313-18292500-2562Human Stem Cells Institute63109710.17816/gc631097ReviewsНаучные обзорыReview ArticleUse of atomic force microscopy to assess the biomechanical properties of 3D tumor cell modelsИспользование атомно-силовой микроскопии для оценки биомеханических свойств 3D-моделей опухолевых клетокhttps://orcid.org/0009-0004-1820-3209PuchkovaKsenia S.ПучковаКсения Сергеевна
Russian Federation
ms.puchkova@yandex.ruhttps://orcid.org/0009-0007-9195-5310LoparevaValeria R.ЛопареваВалерия Романовна
Russian Federation
gontar_78@mail.ruhttps://orcid.org/0009-0005-9628-7492ShepelevaEkaterina V.ШепелеваЕкатерина Владимировна
Russian Federation
plokatyayay@mail.ruhttps://orcid.org/0009-0006-8292-7951MagomedovaOksana A.МагомедоваОксана Арсеновна
Russian Federation
oksana.mag1998@mail.ruhttps://orcid.org/0009-0001-0616-2444IvanovaDaria V.ИвановаДарья Вячеславовна
Russian Federation
dar.ivanova22@gmail.comhttps://orcid.org/0009-0005-8689-4029ZamskayaYulia V.ЗамскаяЮлия Владимировна
Russian Federation
Y.Fom00@mail.ruN.I. Pirogov Russian National Research Medical UniversityРоссийский национальный исследовательский медицинский университет имени Н.И. Пирогова19082024200920241933483582504202409072024Copyright ©; 2024, Eco-VectorCopyright ©; 2024, Эко-Вектор2024Eco-VectorЭко-Векторhttps://creativecommons.org/licenses/by-nc-nd/4.0/https://genescells.ru/2313-1829/article/view/631097

Multicellular spheroids are a unique object model for toxicological studies. Cells in a three-dimensional (3D) cluster contain a microenvironment and intercellular communication, which allows spheroids to be used as a more realistic model than traditional cell cultures. Tumor microregions consist of heterogeneous populations of cancer cells, in which cell growth and response to antitumor drugs depend on their 3D architecture, intercellular contacts, and interaction with the microenvironment. Tumor growth and progression are also strongly influenced by mechanical cues. Currently, 3D cell culture models are powerful tools for studying the toxicity of drug compounds and nanomaterials of different compositions and morphologies.

This review presents data on the use of various techniques, particularly atomic force microscopy, to investigate changes in the mechanical properties of cells in spheroids. Specifically, the use of atomic force microscopy as a tool to reveal physicochemical parameters of cells during pathophysiological processes or drug exposure is considered. The relevance of this review is attributed to the increasing interest in the role of biomechanical properties of tissues, cells, and subcellular structures as markers of pathophysiological conditions.

Многоклеточные сфероиды являются уникальным объектом-моделью для токсикологических исследований. Клетки в 3D-кластере имеют микроокружение, межклеточные коммуникации, что позволяет использовать сфероиды в качестве более реалистичной модели по сравнению с традиционными клеточными культурами. Известно, что микрорегионы опухоли состоят из гетерогенных популяций раковых клеток, в которых рост клеток и ответ на противоопухолевые препараты зависят от их 3D-архитектуры, межклеточных контактов и взаимодействия с микроокружением. Кроме того, на рост и прогрессию опухоли оказывают сильное влияние механические сигналы. В настоящее время 3D-модели клеточных культур являются мощным инструментом для изучения токсичности лекарственных соединений и наноматериалов разного состава и морфологии.

В обзоре представлены данные об использовании различных методик, в частности атомно-силовой микроскопии, для исследования изменений механических свойств клеток в сфероидах. В частности, рассматривается использование атомно-силовой микроскопии как инструмента для выявления физико-химических параметров клеток при патофизиологических процессах или воздействии лекарственных препаратов. Актуальность данного обзора связана с возрастающим интересом к роли биомеханических свойств тканей, клеток и субклеточных структур как маркёров патофизиологических состояний.

spheroidsatomic force microscopynanomechanical propertiesnanotoxicologycancer cellsсфероидыатомно-силовая микросокпиянаномеханические свойствананотоксикологияраковые клеткиGkretsi V, Stylianou A, Papageorgis P, et al. Remodeling components of the tumor microenvironment to enhance cancer therapy. Front Oncol. 2015;5:214. doi: 10.3389/fonc.2015.00214Gkretsi V., Stylianou A., Papageorgis P., et al. remodeling components of the tumor microenvironment to enhance cancer therapy // Front Oncol. 2015. Vol. 5. P. 214. doi: 10.3389/fonc.2015.00214Walker C, Mojares E, Del Río Hernández A. Role of extracellular matrix in development and cancer progression. Int J Mol Sci. 2018;19(10):3028. doi: 10.3390/ijms19103028Walker C., Mojares E., del Río Hernández A. Role of extracellular matrix in development and cancer progression // Int J Mol Sci. 2018. Vol. 19, N 10. P. 3028. doi: 10.3390/ijms19103028Perut F, Sbrana FV, Avnet S, et al. Spheroid-based 3D cell cultures identify salinomycin as a promising drug for the treatment of chondrosarcoma. J Orthop Res. 2018;36:2305–2312. doi: 10.1002/jor.23880Perut F., Sbrana F.V., Avnet S., et al. Spheroid-based 3D cell cultures identify salinomycin as a promising drug for the treatment of chondrosarcoma // Journal of Orthopaedic Research. 2018. Vol. 36. P. 2305–2312. doi: 10.1002/jor.23880Edmondson R, Adcock AF, Yang L. Influence of matrices on 3D-cultured prostate cancer cells’ drug response and expression of drug-action associated proteins. PLoS One. 2016;11(6):e0158116. doi: 10.1371/journal.pone.0158116Edmondson R., Adcock A.F., Yang L. Influence of matrices on 3D-cultured prostate cancer cells’ drug response and expression of drug-action associated proteins // PLoS One. 2016. Vol. 11, N 6. P. e0158116. doi: 10.1371/journal.pone.0158116Tarin D. Role of the host stroma in cancer and its therapeutic significance. Cancer Metastasis Rev. 2013;32(3-4):553–566. doi: 10.1007/s10555-013-9438-4Tarin D. Role of the host stroma in cancer and its therapeutic significance // Cancer Metastasis Rev. 2013. Vol. 32, N 3-4. P. 553–566. doi: 10.1007/s10555-013-9438-4Jain RK, Martin JD, Stylianopoulos T. The role of mechanical forces in tumor growth and therapy. Annu Rev Biomed Eng. 2014;16:321–346. doi: 10.1146/annurev-bioeng-071813-105259Jain R.K., Martin J.D., Stylianopoulos T. The role of mechanical forces in tumor growth and therapy // Annu Rev Biomed Eng. 2014. Vol. 16. P. 321–346. doi: 10.1146/annurev-bioeng-071813-105259Bregenzer ME, Horst EN, Mehta P, et al. Tumor modeling maintains diverse pathology in vitro. Ann Transl Med. 2019;7(Suppl. 8). doi: 10.21037/atm.2019.12.32Bregenzer M.E., Horst E.N., Mehta P., et al. Tumor modeling maintains diverse pathology in vitro // Ann Transl Med. 2019. Vol. 7, Suppl. 8. doi: 10.21037/atm.2019.12.32Hirschhaeuser F, Menne H, Dittfeld C, et al. Multicellular tumor spheroids: an underestimated tool is catching up again. J Biotechnol. 2010;148(1):3–15. doi: 10.1016/j.jbiotec.2010.01.012Hirschhaeuser F., Menne H., Dittfeld C., et al. Multicellular tumor spheroids: an underestimated tool is catching up again // J Biotechnol. 2010. Vol. 148, N 1. P. 3–15. doi: 10.1016/j.jbiotec.2010.01.012Sant S, Johnston PA. The production of 3D tumor spheroids for cancer drug discovery. Drug Discov Today Technol. 2017;23:27–36. doi: 10.1016/j.ddtec.2017.03.002Sant S., Johnston P.A. The production of 3D tumor spheroids for cancer drug discovery // Drug Discov Today Technol. 2017. Vol. 23. P. 27–36. doi: 10.1016/j.ddtec.2017.03.002Białkowska K, Komorowski P, Bryszewska M, Miłowska K. Spheroids as a type of three-dimensional cell cultures-examples of methods of preparation and the most important application. Int J Mol Sci. 2020;21(17):6225. doi: 10.3390/ijms21176225Białkowska K., Komorowski P., Bryszewska M., Miłowska K. Spheroids as a type of three-dimensional cell cultures — examples of methods of preparation and the most important application // Int J Mol Sci. 2020. Vol. 21, N 17. P. 6225. doi: 10.3390/ijms21176225Pinto B, Henriques AC, Silva PMA, Bousbaa H. Three-dimensional spheroids as in vitro preclinical models for cancer research. Pharmaceutics. 2020;12(12):1186. doi: 10.3390/pharmaceutics12121186Pinto B., Henriques A.C., Silva P.M.A., Bousbaa H. Three-dimensional spheroids as in vitro preclinical models for cancer research // Pharmaceutics. 2020. Vol. 12, N 12. P. 1186. doi: 10.3390/pharmaceutics12121186Zanoni M, Cortesi M, Zamagni A, et al. Modeling neoplastic disease with spheroids and organoids. J Hematol Oncol. 2020;13(1):97. doi: 10.1186/s13045-020-00931-0Zanoni M., Cortesi M., Zamagni A., et al. Modeling neoplastic disease with spheroids and organoids // J Hematol Oncol. 2020. Vol. 13, N 1. P. 97. doi: 10.1186/s13045-020-00931-0Han SJ, Kwon S, Kim KS. Challenges of applying multicellular tumor spheroids in preclinical phase. Cancer Cell Int. 2021;21(1):152. doi: 10.1186/s12935-021-01853-8Han S.J., Kwon S., Kim K.S. Challenges of applying multicellular tumor spheroids in preclinical phase // Cancer Cell Int. 2021. Vol. 21, N 1. P. 152. doi: 10.1186/s12935-021-01853-8Wen S, Tu X, Zang Q, et al. Liquid chromatography-mass spectrometry-based metabolomics and fluxomics reveals the metabolic alterations in glioma U87MG multicellular tumor spheroids versus two-dimensional cell cultures. Rapid Commun Mass Spectrom. 2024;38(2):e9670. doi: 10.1002/rcm.9670Wen S., Tu X., Zang Q., et al. Liquid chromatography-mass spectrometry-based metabolomics and fluxomics reveals the metabolic alterations in glioma U87MG multicellular tumor spheroids versus two-dimensional cell cultures // Rapid Commun Mass Spectrom. 2024. Vol. 38, N 2. P. e9670. doi: 10.1002/rcm.9670Desmaison A, Guillaume L, Triclin S, et al. Impact of physical confinement on nuclei geometry and cell division dynamics in 3D spheroids. Sci Rep. 2018;8(1):8785. doi: 10.1038/s41598-018-27060-6Desmaison A., Guillaume L., Triclin S., et al. Impact of physical confinement on nuclei geometry and cell division dynamics in 3D spheroids // Sci Rep. 2018. Vol. 8, N 1. P. 8785. doi: 10.1038/s41598-018-27060-6Lekka M, Gil D, Pogoda K, et al. Cancer cell detection in tissue sections using AFM. Arch Biochem Biophys. 2012;518(2):151–156. doi: 10.1016/j.abb.2011.12.013Lekka M., Gil D., Pogoda K., et al. Cancer cell detection in tissue sections using AFM // Arch Biochem Biophys. 2012. Vol. 518, N 2. P. 151–156. doi: 10.1016/j.abb.2011.12.013Stylianou A, Kontomaris SV, Grant C, Alexandratou E. Atomic force microscopy on biological materials related to pathological conditions. Scanning. 2019;2019:8452851. doi: 10.1155/2019/8452851Stylianou A., Kontomaris S.V., Grant C., Alexandratou E. Atomic force microscopy on biological materials related to pathological conditions // Scanning. 2019. Vol. 2019. P. 8452851. doi: 10.1155/2019/8452851Runel G, Lopez-Ramirez N, Chlasta J, Masse I. Biomechanical properties of cancer cells. Cells. 2021;10(4):887. doi: 10.3390/cells10040887Runel G., Lopez-Ramirez N., Chlasta J., Masse I. Biomechanical properties of cancer cells // Cells. 2021. Vol. 10, N 4. P. 887. doi: 10.3390/cells10040887Chowdhury F, Na S, Li D, et al. Material properties of the cell dictate stress-induced spreading and differentiation in embryonic stem cells. Nat Mater. 2010;9(1):82–88. doi: 10.1038/nmat2563Chowdhury F., Na S., Li D., et al. Material properties of the cell dictate stress-induced spreading and differentiation in embryonic stem cells // Nat Mater. 2010. Vol. 9, N 1. P. 82–88. doi: 10.1038/nmat2563Docheva D, Padula D, Popov C, et al. Researching into the cellular shape, volume and elasticity of mesenchymal stem cells, osteoblasts and osteosarcoma cells by atomic force microscopy. J Cell Mol Med. 2008;12(2):537–552. doi: 10.1111/j.1582-4934.2007.00138.xDocheva D., Padula D., Popov C., et al. Researching into the cellular shape, volume and elasticity of mesenchymal stem cells, osteoblasts and osteosarcoma cells by atomic force microscopy // J Cell Mol Med. 2008. Vol. 12, N 2. P. 537–552. doi: 10.1111/j.1582-4934.2007.00138.xSuresh S. Biomechanics and biophysics of cancer cells. Acta Biomater. 2007;3(4):413–438. doi: 10.1016/j.actbio.2007.04.002Suresh S. Biomechanics and biophysics of cancer cells // Acta Biomater. 2007. Vol. 3, N 4. P. 413–438. doi: 10.1016/j.actbio.2007.04.002Li QS, Lee GY, Ong CN, Lim CT. AFM indentation study of breast cancer cells. Biochem Biophys Res Commun. 2008;374(4):609–613. doi: 10.1016/j.bbrc.2008.07.078Li Q.S., Lee G.Y., Ong C.N., Lim C.T. AFM indentation study of breast cancer cells // Biochem Biophys Res Commun. 2008. Vol. 374, N 4. P. 609–613. doi: 10.1016/j.bbrc.2008.07.078Nia HT, Munn LL, Jain RK. Physical traits of cancer. Science. 2020;370(6516):eaaz0868. doi: 10.1126/science.aaz0868Nia H.T., Munn L.L., Jain R.K. Physical traits of cancer // Science. 2020. Vol. 370, N 6516. P. eaaz0868. doi: 10.1126/science.aaz0868Pi J, Cai J. Cell Topography and its quantitative imaging by AFM. Methods Mol Biol. 2019;1886:99–113. doi: 10.1007/978-1-4939-8894-5_6Pi J., Cai J. Cell topography and its quantitative imaging by AFM // Methods Mol Biol. 2019. Vol. 1886. P. 99–113. doi: 10.1007/978-1-4939-8894-5_6Vargo-Gogola T, Rosen JM. Modelling breast cancer: one size does not fit all. Nat Rev Cancer. 2007;7(9):659–672. doi: 10.1038/nrc2193Vargo-Gogola T., Rosen J.M. Modelling breast cancer: one size does not fit all // Nat Rev Cancer. 2007. Vol. 7, N 9. P. 659–672. doi: 10.1038/nrc2193Correia AL, Bissell MJ. The tumor microenvironment is a dominant force in multidrug resistance. Drug Resist Updat. 2012;15(1-2):39–49. doi: 10.1016/j.drup.2012.01.006Correia A.L., Bissell M.J. The tumor microenvironment is a dominant force in multidrug resistance // Drug Resist Updat. 2012. Vol. 15, N 1-2. P. 39–49. doi: 10.1016/j.drup.2012.01.006Meads MB, Gatenby RA, Dalton WS. Environment-mediated drug resistance: a major contributor to minimal residual disease. Nat Rev Cancer. 2009;9(9):665–674. doi: 10.1038/nrc2714Meads M.B., Gatenby R.A., Dalton W.S. Environment-mediated drug resistance: a major contributor to minimal residual disease // Nat Rev Cancer. 2009. Vol. 9, N 9. P. 665–674. doi: 10.1038/nrc2714Bhatia SN, Chen CS. Tissue engineering at the micro-scale. Biomedical Microdevices. 1999;2:131–144. doi: 10.1023/A:1009949704750Bhatia S.N., Chen C.S. Tissue engineering at the micro-scale // Biomedical Microdevices. 1999. Vol. 2. P. 131–144. doi: 10.1023/A:1009949704750Centeno EGZ, Cimarosti H, Bithell A. 2D versus 3D human induced pluripotent stem cell-derived cultures for neurodegenerative disease modelling. Mol Neurodegener. 2018;13(1):27. doi: 10.1186/s13024-018-0258-4Centeno E.G.Z., Cimarosti H., Bithell A. 2D versus 3D human induced pluripotent stem cell-derived cultures for neurodegenerative disease modeling // Mol Neurodegener. 2018. Vol. 13, N 1. P. 27. doi: 10.1186/s13024-018-0258-4Goodman TT, Ng CP, Pun SH. 3-D tissue culture systems for the evaluation and optimization of nanoparticle-based drug carriers. Bioconjug Chem. 2008;19(10):1951–1959. doi: 10.1021/bc800233aGoodman T.T., Ng C.P., Pun S.H. 3-D tissue culture systems for the evaluation and optimization of nanoparticle-based drug carriers // Bioconjug Chem. 2008. Vol. 19, N 10. P. 1951–1959. doi: 10.1021/bc800233aLee J, Lilly GD, Doty RC, et al. In vitro toxicity testing of nanoparticles in 3D cell culture. Small. 2009;5(10):1213–1221. doi: 10.1002/smll.200801788Lee J., Lilly G.D., Doty R.C., et al. In vitro toxicity testing of nanoparticles in 3D cell culture // Small. 2009. Vol. 5, N 10. P. 1213–1221. doi: 10.1002/smll.200801788Moshksayan K, Kashaninejad N, Warkiani ME, et al. Spheroids-on-a-chip: Recent advances and design considerations in microfluidic platforms for spheroid formation and culture. Sensors and Actuators B: Chemical. 2018;263:151–176. doi: 10.1016/j.snb.2018.01.223Moshksayan K., Kashaninejad N., Warkiani M.E., et al. Spheroids-on-a-chip: Recent advances and design considerations in microfluidic platforms for spheroid formation and culture // Sensors and Actuators B: Chemical. 2018. Vol. 263. P. 151–176. doi: 10.1016/j.snb.2018.01.223Edmondson R, Broglie JJ, Adcock AF, Yang L. Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors. Assay Drug Dev Technol. 2014;12(4):207–218. doi: 10.1089/adt.2014.573Edmondson R., Broglie J.J., Adcock A.F., Yang L. Three-dimensional cell culture systems and their applications in drug discovery and cell-based biosensors // Assay Drug Dev Technol. 2014. Vol. 12, N 4. P. 207–218. doi: 10.1089/adt.2014.573Bregenzer ME, Horst EN, Mehta P, et al. Integrated cancer tissue engineering models for precision medicine. PLoS One. 2019;14(5):e0216564. doi: 10.1371/journal.pone.0216564Bregenzer M.E., Horst E.N., Mehta P., et al. Integrated cancer tissue engineering models for precision medicine // PLoS One. 2019. Vol. 14, N 5. P. e0216564. doi: 10.1371/journal.pone.0216564Kosheleva NV, Efremov YM, Koteneva PI, et al. Building a tissue: Mesenchymal and epithelial cell spheroids mechanical properties at micro- and nanoscale. Acta Biomater. 2023;165:140–152. doi: 10.1016/j.actbio.2022.09.051Kosheleva N.V., Efremov Y.M., Koteneva P.I., et al. Building a tissue: Mesenchymal and epithelial cell spheroids mechanical properties at micro- and nanoscale // Acta Biomater. 2023. Vol. 165. P. 140–152. doi: 10.1016/j.actbio.2022.09.051Nunes AS, Barros AS, Costa EC, et al. 3D tumor spheroids as in vitro models to mimic in vivo human solid tumors resistance to therapeutic drugs. Biotechnol Bioeng. 2019;116(1):206–226. doi: 10.1002/bit.26845Nunes A.S., Barros A.S., Costa E.C., et al. 3D tumor spheroids as in vitro models to mimic in vivo human solid tumors resistance to therapeutic drugs // Biotechnol Bioeng. 2019. Vol. 116, N 1. P. 206–226. doi: 10.1002/bit.26845Nath S, Devi GR. Three-dimensional culture systems in cancer research: Focus on tumor spheroid model. Pharmacol Ther. 2016;163:94–108. doi: 10.1016/j.pharmthera.2016.03.013Nath S., Devi G.R. Three-dimensional culture systems in cancer research: Focus on tumor spheroid model // Pharmacol Ther. 2016. Vol. 163. P. 94–108. doi: 10.1016/j.pharmthera.2016.03.013Laurent J, Frongia C, Cazales M, et al. Multicellular tumor spheroid models to explore cell cycle checkpoints in 3D. BMC Cancer. 2013;13:73. doi: 10.1186/1471-2407-13-73Laurent J., Frongia C., Cazales M., et al. Multicellular tumor spheroid models to explore cell cycle checkpoints in 3D // BMC Cancer. 2013. Vol. 13. P. 73. doi: 10.1186/1471-2407-13-73Riffle S, Pandey RN, Albert M, Hegde RS. Linking hypoxia, DNA damage and proliferation in multicellular tumor spheroids. BMC Cancer. 2017;17(1):338. doi: 10.1186/s12885-017-3319-0Riffle S., Pandey R.N., Albert M., Hegde R.S. Linking hypoxia, DNA damage and proliferation in multicellular tumor spheroids // BMC Cancer. 2017. Vol. 17, N 1. P. 338. doi: 10.1186/s12885-017-3319-0Riffle S, Hegde RS. Modeling tumor cell adaptations to hypoxia in multicellular tumor spheroids. J Exp Clin Cancer Res. 2017;36(1):102. doi: 10.1186/s13046-017-0570-9Riffle S., Hegde R.S. Modeling tumor cell adaptations to hypoxia in multicellular tumor spheroids // J Exp Clin Cancer Res. 2017. Vol. 36, N 1. P. 102. doi: 10.1186/s13046-017-0570-9Ong SM, Zhao Z, Arooz T, et al. Engineering a scaffold-free 3D tumor model for in vitro drug penetration studies. Biomaterials. 2010;31(6):1180–1190. doi: 10.1016/j.biomaterials.2009.10.049Ong S.M., Zhao Z., Arooz T., et al. Engineering a scaffold-free 3D tumor model for in vitro drug penetration studies // Biomaterials. 2010. Vol. 31, N 6. P. 1180–1190. doi: 10.1016/j.biomaterials.2009.10.049Pokharel D, Wijesinghe P, Oenarto V, et al. Deciphering cell-to-cell communication in acquisition of cancer traits: extracellular membrane vesicles are regulators of tissue biomechanics. OMICS. 2016;20(8):462–469. doi: 10.1089/omi.2016.0072Pokharel D., Wijesinghe P., Oenarto V., et al. Deciphering cell-to-cell communication in acquisition of cancer traits: extracellular membrane vesicles are regulators of tissue biomechanics // OMICS. 2016. Vol. 20, N 8. P. 462–469. doi: 10.1089/omi.2016.0072Conrad CB. Mechanical adaptability of ovarian cancer tumor spheroids [dissertation]. 2021. doi: 10.13016/yl6l-abpuConrad C.B. Mechanical adaptability of ovarian cancer tumor spheroids [dissertation]. 2021. doi: 10.13016/yl6l-abpuJaiswal D, Moscato Z, Tomizawa Y, et al. Elastography of multicellular spheroids using 3D light microscopy. Biomed Opt Express. 2019;10(5):2409–2418. doi: 10.1364/BOE.10.002409Jaiswal D., Moscato Z., Tomizawa Y., et al. Elastography of multicellular spheroids using 3D light microscopy // Biomed Opt Express. 2019. Vol. 10, N 5. P. 2409–2418. doi: 10.1364/BOE.10.002409Hansen O, Magonov S, Su C, et al. Discerning biomolecular interactions using kelvin probe technology. Langmuir. 2003;19(18):7514–7520. doi: 10.1021/la034333wHansen D.C., Hansen K.M., Ferrell T.L., Thundat T. Discerning biomolecular interactions using kelvin probe technology // Langmuir. 2003. Vol. 19, N 18. P. 7514–7520. doi: 10.1021/la034333wSahin O, Magonov S, Su C, et al. An atomic force microscope tip designed to measure time-varying nanomechanical forces. Nat Nanotechnol. 2007;2(8):507–514. doi: 10.1038/nnano.2007.226Sahin O., Magonov S., Su C., et al. An atomic force microscope tip designed to measure time-varying nanomechanical forces // Nat Nanotechnol. 2007. Vol. 2, N 8. P. 507–514. doi: 10.1038/nnano.2007.226Chen D, Gan H, Huang X, et al. Effects of peripheral blood mononuclear cells morphology on vascular calcification in uremic patients on maintenance hemodialysis. Ther Apher Dial. 2012;16(2):173–180. doi: 10.1111/j.1744-9987.2011.01044.xChen D., Gan H., Huang X., et al. Effects of peripheral blood mononuclear cells morphology on vascular calcification in uremic patients on maintenance hemodialysis // Ther Apher Dial. 2012. Vol. 16, N 2. P. 173–180. doi: 10.1111/j.1744-9987.2011.01044.xJin H, Xing X, Zhao H, et al. Detection of erythrocytes influenced by aging and type 2 diabetes using atomic force microscope. Biochem Biophys Res Commun. 2010;391(4):1698–1702. doi: 10.1016/j.bbrc.2009.12.133Jin H., Xing X., Zhao H., et al. Detection of erythrocytes influenced by aging and type 2 diabetes using atomic force microscope // Biochem Biophys Res Commun. 2010. Vol. 391, N 4. P. 1698–1702. doi: 10.1016/j.bbrc.2009.12.133Zhang Y, Zhang W, Wang S, et al. Detection of erythrocytes in patients with multiple myeloma using atomic force microscopy. Scanning. 2012;34(5):295–301. doi: 10.1002/sca.21008Zhang Y., Zhang W., Wang S., et al. Detection of erythrocytes in patients with multiple myeloma using atomic force microscopy // Scanning. 2012. Vol. 34, N 5. P. 295–301. doi: 10.1002/sca.21008Zhang Y, Zhang W, Wang S, et al. Detection of erythrocytes in patient with iron deficiency anemia using atomic force microscopy. Scanning. 2012;34(4):215–220. doi: 10.1002/sca.20296Zhang Y., Zhang W., Wang S., et al. Detection of erythrocytes in patient with iron deficiency anemia using atomic force microscopy // Scanning. 2012. Vol. 34, N 4. P. 215–220. doi: 10.1002/sca.20296Fang Y, Iu CY, Lui CN, et al. Investigating dynamic structural and mechanical changes of neuroblastoma cells associated with glutamate-mediated neurodegeneration. Sci Rep. 2014;4:7074. doi: 10.1038/srep07074Fang Y., Iu C.Y., Lui C.N., et al. Investigating dynamic structural and mechanical changes of neuroblastoma cells associated with glutamate-mediated neurodegeneration // Sci Rep. 2014. Vol. 4. P. 7074. doi: 10.1038/srep07074Kim KS, Cho CH, Park EK, et al. AFM-detected apoptotic changes in morphology and biophysical property caused by paclitaxel in Ishikawa and HeLa cells. PLoS One. 2012;7(1):e30066. doi: 10.1371/journal.pone.0030066Kim K.S., Cho C.H., Park E.K., et al. AFM-detected apoptotic changes in morphology and biophysical property caused by paclitaxel in Ishikawa and HeLa cells // PLoS One. 2012. Vol. 7, N 1. P. e30066. doi: 10.1371/journal.pone.0030066Chen M, Zeng J, Ruan W, et al. Examination of the relationship between viscoelastic properties and the invasion of ovarian cancer cells by atomic force microscopy. Beilstein J Nanotechnol. 2020;11:568–582. doi: 10.3762/bjnano.11.45Chen M., Zeng J., Ruan W., et al. Examination of the relationship between viscoelastic properties and the invasion of ovarian cancer cells by atomic force microscopy // Beilstein J Nanotechnol. 2020. Vol. 11. P. 568–582. doi: 10.3762/bjnano.11.45Lian S, Shi R, Huang X, et al. Artesunate attenuates glioma proliferation, migration and invasion by affecting cellular mechanical properties. Oncol Rep. 2016;36(2):984–990. doi: 10.3892/or.2016.4847Lian S., Shi R., Huang X., et al. Artesunate attenuates glioma proliferation, migration and invasion by affecting cellular mechanical properties // Oncol Rep. 2016. Vol. 36, N 2. P. 984–990. doi: 10.3892/or.2016.4847Zhang L, Yang F, Cai JY, et al. In-situ detection of resveratrol inhibition effect on epidermal growth factor receptor of living MCF-7 cells by atomic force microscopy. Biosens Bioelectron. 2014;56:271–277. doi: 10.1016/j.bios.2014.01.024Zhang L., Yang F., Cai J.Y., et al. In-situ detection of resveratrol inhibition effect on epidermal growth factor receptor of living MCF-7 cells by atomic force microscopy // Biosens Bioelectron. 2014. Vol. 56. P. 271–277. doi: 10.1016/j.bios.2014.01.024Pi J, Li B, Tu L, et al. Investigation of quercetin-induced HepG2 cell apoptosis-associated cellular biophysical alterations by atomic force microscopy. Scanning. 2016;38(2):100–112. doi: 10.1002/sca.21245Pi J., Li B., Tu L., et al. Investigation of quercetin-induced HepG2 cell apoptosis-associated cellular biophysical alterations by atomic force microscopy // Scanning. 2016. Vol. 38, N 2. P. 100–112. doi: 10.1002/sca.21245Wang J, Wan Z, Liu W, et al. Atomic force microscope study of tumor cell membranes following treatment with anti-cancer drugs. Biosens Bioelectron. 2009;25(4):721–727. doi: 10.1016/j.bios.2009.08.011Wang J., Wan Z., Liu W., et al. Atomic force microscope study of tumor cell membranes following treatment with anti-cancer drugs // Biosens Bioelectron. 2009. Vol. 25, N 4. P. 721–727. doi: 10.1016/j.bios.2009.08.011Cambria E, Coughlin MF, Floryan MA, et al. Linking cell mechanical memory and cancer metastasis. Nat Rev Cancer. 2024;24(3):216–228. doi: 10.1038/s41568-023-00656-5Cambria E., Coughlin M.F., Floryan M.A., et al. Linking cell mechanical memory and cancer metastasis // Nat Rev Cancer. 2024. Vol. 24, N 3. P. 216–228. doi: 10.1038/s41568-023-00656-5Müller DJ, Helenius J, Alsteens D, Dufrêne YF. Force probing surfaces of living cells to molecular resolution. Nat Chem Biol. 2009;5(6):383–390. doi: 10.1038/nchembio.181Müller D.J., Helenius J., Alsteens D., Dufrêne Y.F. Force probing surfaces of living cells to molecular resolution // Nat Chem Biol. 2009. Vol. 5, N 6. P. 383–390. doi: 10.1038/nchembio.181Haase K, Pelling AE. Investigating cell mechanics with atomic force microscopy. J R Soc Interface. 2015;12(104):20140970. doi: 10.1098/rsif.2014.0970Haase K., Pelling A.E. Investigating cell mechanics with atomic force microscopy // J R Soc Interface. 2015. Vol. 12, N 104. P. 20140970. doi: 10.1098/rsif.2014.0970Müller DJ, Dufrêne YF. Atomic force microscopy as a multifunctional molecular toolbox in nanobiotechnology. Nat Nanotechnol. 2008;3(5):261–269. doi: 10.1038/nnano.2008.100Müller D.J., Dufrêne Y.F. Atomic force microscopy as a multifunctional molecular toolbox in nanobiotechnology // Nat Nanotechnol. 2008. Vol. 3, N 5. P. 261–269. doi: 10.1038/nnano.2008.100Schillers H, Rianna C, Schäpe J, et al. Standardized nanomechanical atomic force microscopy procedure (snap) for measuring soft and biological samples. Sci Rep. 2017;7(1):5117. doi: 10.1038/s41598-017-05383-0Schillers H., Rianna C., Schäpe J., et al. Standardized nanomechanical atomic force microscopy procedure (snap) for measuring soft and biological samples // Sci Rep. 2017. Vol. 7, N 1. P. 5117. doi: 10.1038/s41598-017-05383-0Andolfi L, Greco SLM, Tierno D, et al. Planar AFM macro-probes to study the biomechanical properties of large cells and 3D cell spheroids. Acta Biomater. 2019;94:505–513. doi: 10.1016/j.actbio.2019.05.072Andolfi L., Greco S.L.M., Tierno D., et al. Planar AFM macro-probes to study the biomechanical properties of large cells and 3D cell spheroids // Acta Biomater. 2019. Vol. 94. P. 505–513. doi: 10.1016/j.actbio.2019.05.072Guillaume L, Rigal L, Fehrenbach J, et al. Characterization of the physical properties of tumor-derived spheroids reveals critical insights for pre-clinical studies. Sci Rep. 2019;9(1):6597. doi: 10.1038/s41598-019-43090-0Guillaume Rigal L., Fehrenbach J., et al. Characterization of the physical properties of tumor-derived spheroids reveals critical insights for pre-clinical studies // Sci Rep. 2019. Vol. 9, N 1. P. 6597. doi: 10.1038/s41598-019-43090-0Gonzalez-Rodriguez D, Guevorkian K, Douezan S, Brochard-Wyart F. Soft matter models of developing tissues and tumors. Science. 2012;338(6109):910–917. doi: 10.1126/science.1226418Gonzalez-Rodriguez D., Guevorkian K., Douezan S., Brochard-Wyart F. Soft matter models of developing tissues and tumors // Science. 2012. Vol. 338, N 6109. P. 910–917. doi: 10.1126/science.1226418Dolega ME, Delarue M, Ingremeau F, et al. Cell-like pressure sensors reveal increase of mechanical stress towards the core of multicellular spheroids under compression. Nat Commun. 2017;8:14056. doi: 10.1038/ncomms14056Dolega M.E., Delarue M., Ingremeau F., et al. Cell-like pressure sensors reveal increase of mechanical stress towards the core of multicellular spheroids under compression // Nat Commun. 2017. Vol. 8. P. 14056. doi: 10.1038/ncomms14056Zhang W, Wang S, Lin M, et al. Advances in experimental approaches for investigating cell aggregate mechanics. Acta Mechanica Solida Sinica. 2012;25:473–482. doi: 10.1016/S0894-9166(12)60042-1Zhang W., Wang S., Lin M., et al. Advances in experimental approaches for investigating cell aggregate mechanics // Acta Mechanica Solida Sinica. 2012. Vol. 25. P. 473–482. doi: 10.1016/S0894-9166(12)60042-1Bhat S, Jun D, Paul B, Dahms T. In Viscoelasticity in biological systems: A special focus on microbes // InTech. 2012. doi: 10.5772/49980Bhat S., Jun D., Paul B., Dahms T. In Viscoelasticity in biological systems: A special focus on microbes // InTech. 2012. doi: 10.5772/49980Sergunova V, Leesment S, Kozlov A, et al. Investigation of red blood cells by atomic force microscopy. Sensors (Basel). 2022;22(5):2055. doi: 10.3390/s22052055Sergunova V., Leesment S., Kozlov A., et al. Investigation of red blood cells by atomic force microscopy // Sensors (Basel). 2022. Vol. 22, N 5. P. 2055. doi: 10.3390/s22052055Stewart MP, Toyoda Y, Hyman AA, Müller DJ. Tracking mechanics and volume of globular cells with atomic force microscopy using a constant-height clamp. Nat Protoc. 2012;7(1):143–154. doi: 10.1038/nprot.2011.434Stewart M., Toyoda Y., Hyman A., Müller D. Tracking mechanics and volume of globular cells with atomic force microscopy using a constant-height clamp // Nat Protoc. 2012. Vol. 7, N 1. P. 143–154. doi: 10.1038/nprot.2011.434Guimarães CF, Gasperini L, Marques AP, Reis RL. The stiffness of living tissues and its implications for tissue engineering. Nature Reviews Materials. 2020:5(5):351–370. doi: 10.1038/s41578-019-0169-1Guimarães C.F., Gasperini L., Marques A.P., Reis R.L. The stiffness of living tissues and its implications for tissue engineering // Nature Reviews Materials. 2020. Vol. 5, N 5. P. 351–370. doi: 10.1038/s41578-019-0169-1Fischer-Friedrich E, Hyman AA, Jülicher F, et al. Quantification of surface tension and internal pressure generated by single mitotic cells. Sci Rep. 2014;4:6213. doi: 10.1038/srep06213Fischer-Friedrich E., Hyman A.A., Jülicher F., et al. Quantification of surface tension and internal pressure generated by single mitotic cells // Sci Rep. 2014. Vol. 4. P. 6213. doi: 10.1038/srep06213Krause M, Te Riet J, Wolf K. Probing the compressibility of tumor cell nuclei by combined atomic force-confocal microscopy. Phys Biol. 2013;10(6):065002. doi: 10.1088/1478-3975/10/6/065002Krause M., Te Riet J., Wolf K. Probing the compressibility of tumor cell nuclei by combined atomic force-confocal microscopy // Phys Biol. 2013. Vol. 10, N 6. P. 065002. doi: 10.1088/1478-3975/10/6/065002Lam WA, Chaudhuri O, Crow A, et al. Mechanics and contraction dynamics of single platelets and implications for clot stiffening. Nat Mater. 2011;10(1):61–66. doi: 10.1038/nmat2903Lam W.A., Chaudhuri O., Crow A., et al. Mechanics and contraction dynamics of single platelets and implications for clot stiffening // Nat Mater. 2011. Vol. 10, N 1. P. 61–66. doi: 10.1038/nmat2903Stewart MP, Helenius J, Toyoda Y, et al. Hydrostatic pressure and the actomyosin cortex drive mitotic cell rounding. Nature. 2019;571(7764):E5. doi: 10.1038/s41586-019-1327-8Stewart M., Helenius J., Toyoda Y., et al. Publisher correction: hydrostatic pressure and the actomyosin cortex drive mitotic cell rounding // Nature. 2019. Vol. 571, N 7764. P. E5. doi: 10.1038/s41586-019-1327-8Viljoen A, Mathelié-Guinlet M, Ray A, et al. Force spectroscopy of single cells using atomic force microscopy. Nat Rev Methods Primers. 2021;1(63):63. doi: 10.1038/s43586-021-00062-xViljoen A., Mathelié-Guinlet M., Ray A., et al. Force spectroscopy of single cells using atomic force microscopy // Nat Rev Methods Primers. 2021. Vol. 1, N 63. P. 63. doi: 10.1038/s43586-021-00062-xStewart MP, Hodel AW, Spielhofer A, et al. Wedged AFM-cantilevers for parallel plate cell mechanics. Methods. 2013;60(2):186–194. doi: 10.1016/j.ymeth.2013.02.015Stewart M.P., Hodel A.W., Spielhofer A., et al. Wedged AFM-cantilevers for parallel plate cell mechanics // Methods. 2013. Vol. 60, N 2. P. 186–194. doi: 10.1016/j.ymeth.2013.02.015Stylianopoulos T, Martin JD, Chauhan VP, et al. Causes, consequences, and remedies for growth-induced solid stress in murine and human tumors. Proc Natl Acad Sci U S A. 2012;109(38):15101–15108. doi: 10.1073/pnas.1213353109Stylianopoulos T., Martin J.D., Chauhan V.P., et al. Causes, consequences, and remedies for growth-induced solid stress in murine and human tumors // Proc Natl Acad Sci U S A. 2012. Vol. 109, N 38. P. 15101–15108. doi: 10.1073/pnas.1213353109Jaiswal D, Cowley N, Bian Z, et al. Stiffness analysis of 3D spheroids using microtweezers. PLoS One. 2017;12(11):e0188346. doi: 10.1371/journal.pone.0188346Jaiswal D., Cowley N., Bian Z., et al. Stiffness analysis of 3D spheroids using microtweezers // PLoS One. 2017. Vol. 12, N 11. P. e0188346. doi: 10.1371/journal.pone.0188346