{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:17:45Z","timestamp":1787807865177,"version":"build-2784847793"},"reference-count":29,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012547","name":"Natural Science Foundation of Guangxi Zhuang Autonomous Region","doi-asserted-by":"crossref","award":["2606020145"],"award-info":[{"award-number":["2606020145"]}],"id":[{"id":"10.13039\/100012547","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100012547","name":"Natural Science Foundation of Guangxi Zhuang Autonomous Region","doi-asserted-by":"crossref","award":["2023GXNSFBA026214"],"award-info":[{"award-number":["2023GXNSFBA026214"]}],"id":[{"id":"10.13039\/100012547","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100012547","name":"Natural Science Foundation of Guangxi Zhuang Autonomous Region","doi-asserted-by":"crossref","award":["2026GXNSFAA00641106"],"award-info":[{"award-number":["2026GXNSFAA00641106"]}],"id":[{"id":"10.13039\/100012547","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62501242"],"award-info":[{"award-number":["62501242"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["62501242"],"award-info":[{"award-number":["62501242"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biosensors"],"abstract":"<jats:p>High-throughput microfluidic deformation assays enable label-free single-cell mechanophenotyping by quantifying how cells deform under controlled hydrodynamic loading. These approaches commonly extract deformation-related observables, such as projected area, axis ratio, and deformation index, and use them as indicators for cellular mechanical properties. However, deformation is not solely determined by stiffness; it is a coupled outcome of cell size, local hydrodynamic stress, and intrinsic mechanical response. Therefore, we present a simulation-based microfluidic framework for estimating region-dependent apparent Young\u2019s modulus (E, a quantitative indicator characterizing cellular mechanical stiffness) from diameter\u2013deformation measurements at the single-cell level. A three-region microfluidic channel is designed to impose distinct hydrodynamic loading conditions, while numerical simulations establish quantitative maps linking cell diameter, deformation, and E. Based on these results, region-specific nonlinear surface models are constructed to invert experimental diameter\u2013deformation measurements into E values. Finally, application to primary T cells and K562 cells demonstrates clear region-dependent differences in E, highlighting the influence of local loading conditions on inferred mechanical properties. Overall, this work provides a simplified but practical route for transforming deformation-based phenotypes into quantitative, loading-aware mechanical parameters for single-cell analysis.<\/jats:p>","DOI":"10.3390\/bios16090461","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T11:27:19Z","timestamp":1787657239000},"page":"461","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Simulation-Based Microfluidic Deformation Mapping for Region-Dependent Apparent Young\u2019s Modulus Estimation of Single Cells"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2577-2405","authenticated-orcid":false,"given":"Minhui","family":"Liang","sequence":"first","affiliation":[{"name":"School of Mechanical Engineering, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilong","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Mechanical Engineering, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawei","family":"Ming","sequence":"additional","affiliation":[{"name":"School of Mechanical Engineering, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Lyu","sequence":"additional","affiliation":[{"name":"School of Mechanical Engineering, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6198-868X","authenticated-orcid":false,"given":"Jianwei","family":"Zhong","sequence":"additional","affiliation":[{"name":"School of Microelectronics, South China University of Technology, Guangzhou 511442, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Li","sequence":"additional","affiliation":[{"name":"The People\u2019s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning 530021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7853-2558","authenticated-orcid":false,"given":"Lin","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Mechanical Engineering, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7630","DOI":"10.1073\/pnas.1200107109","article-title":"Hydrodynamic stretching of single cells for large population mechanical phenotyping","volume":"109","author":"Gossett","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1002\/cm.21369","article-title":"High-throughput cell mechanical phenotyping for label-free titration assays of cytoskeletal modifications","volume":"74","author":"Golfier","year":"2017","journal-title":"Cytoskeleton"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/nmeth.3281","article-title":"Real-time deformability cytometry: On-the-fly cell mechanical phenotyping","volume":"12","author":"Otto","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/s41592-020-0818-8","article-title":"A comparison of microfluidic methods for high-throughput cell deformability measurements","volume":"17","author":"Urbanska","year":"2020","journal-title":"Nat. Methods"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.bpj.2015.05.029","article-title":"Microconstriction arrays for high-throughput quantitative measurements of cell mechanical properties","volume":"109","author":"Lange","year":"2015","journal-title":"Biophys. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1700705","DOI":"10.1002\/smll.201700705","article-title":"Inertial microfluidic cell stretcher (iMCS): Fully automated, high-throughput, and near real-time cell mechanotyping","volume":"13","author":"Deng","year":"2017","journal-title":"Small"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/s41378-024-00810-5","article-title":"Single-cell electro-mechanical shear flow deformability cytometry","volume":"10","author":"Chen","year":"2024","journal-title":"Microsyst. Nanoeng."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"eabj1133","DOI":"10.1126\/sciadv.abj1133","article-title":"Real-time viscoelastic deformability cytometry: High-throughput mechanical phenotyping of liquid and solid biopsies","volume":"10","author":"Asghari","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2104822","DOI":"10.1002\/smll.202104822","article-title":"Microfluidic impedance-deformability cytometry for label-free single neutrophil mechanophenotyping","volume":"18","author":"Petchakup","year":"2022","journal-title":"Small"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2200325","DOI":"10.1002\/smtd.202200325","article-title":"Impedance-enabled camera-free intrinsic mechanical cytometry","volume":"6","author":"Feng","year":"2022","journal-title":"Small Methods"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"014104","DOI":"10.1063\/5.0077432","article-title":"Deep learning assisted mechanotyping of individual cells through repeated deformations and relaxations in undulating channels","volume":"16","author":"Combs","year":"2022","journal-title":"Biomicrofluidics"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"7580","DOI":"10.1073\/pnas.1218806110","article-title":"Characterizing deformability and surface friction of cancer cells","volume":"110","author":"Byun","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2200628","DOI":"10.1002\/adhm.202200628","article-title":"A systematic study of size correlation and Young\u2019s modulus sensitivity for cellular mechanical phenotyping by microfluidic approaches","volume":"11","author":"Liang","year":"2022","journal-title":"Adv. Healthc. Mater."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1146\/annurev.bioeng.10.061807.160511","article-title":"Cell mechanics: Dissecting the physical responses of cells to force","volume":"11","author":"Hoffman","year":"2009","journal-title":"Annu. Rev. Biomed. Eng."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1083\/jcb.113.1.155","article-title":"Viscoelastic properties of vimentin compared with other filamentous biopolymer networks","volume":"113","author":"Janmey","year":"1991","journal-title":"J. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3774","DOI":"10.1039\/c2lc40477j","article-title":"Nuclear deformation during breast cancer cell transmigration","volume":"12","author":"Fu","year":"2012","journal-title":"Lab Chip"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.tcb.2012.07.001","article-title":"Actin cortex mechanics and cellular morphogenesis","volume":"22","author":"Salbreux","year":"2012","journal-title":"Trends Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6213","DOI":"10.1038\/srep06213","article-title":"Quantification of surface tension and internal pressure generated by single mitotic cells","volume":"4","author":"Hyman","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1016\/j.bpj.2015.03.047","article-title":"Human primary immune cells exhibit distinct mechanical properties that are modified by inflammation","volume":"108","author":"Bufi","year":"2015","journal-title":"Biophys. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1016\/j.bpj.2021.02.042","article-title":"Rapid viscoelastic changes are a hallmark of early leukocyte activation","volume":"120","author":"Zak","year":"2021","journal-title":"Biophys. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1016\/j.bpj.2015.09.006","article-title":"Extracting cell stiffness from real-time deformability cytometry: Theory and experiment","volume":"109","author":"Mietke","year":"2015","journal-title":"Biophys. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4567","DOI":"10.1021\/acs.analchem.0c05009","article-title":"Single-cell stretching in viscoelastic fluids with electronically triggered imaging for cellular mechanical phenotyping","volume":"93","author":"Liang","year":"2021","journal-title":"Anal. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1892","DOI":"10.1039\/c3lc50074h","article-title":"Droplet morphometry and velocimetry (DMV): A video processing software for time-resolved, label-free tracking of droplet parameters","volume":"13","author":"Basu","year":"2013","journal-title":"Lab Chip"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"115086","DOI":"10.1016\/j.bios.2023.115086","article-title":"Machine learning empowered multi-stress level electromechanical phenotyping for high-dimensional single cell analysis","volume":"225","author":"Liang","year":"2023","journal-title":"Biosens. Bioelectron."},{"key":"ref_25","unstructured":"Calzado-Martin, A., Zhou, X., Iden, S., Bischoff, M., and Qu, B. (2021). T cell stiffness is enhanced upon formation of immunological synapse. Front. Cell Dev. Biol., 9."},{"key":"ref_26","first-page":"86","article-title":"AFM indentation characterization of mechanical heterogeneity in suspended K562 myeloid leukemia cells","volume":"19","author":"Li","year":"2020","journal-title":"Biomed. Eng. Online"},{"key":"ref_27","first-page":"19563","article-title":"Mechanical phenotyping of K562 cells by the Micropipette Aspiration Technique allows identifying mechanical changes induced by drugs","volume":"8","author":"Puggioni","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2962","DOI":"10.1021\/acsbiomaterials.6b00558","article-title":"Numerical simulation of real-time deformability cytometry to extract cell mechanical properties","volume":"3","author":"Mokbel","year":"2017","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"15696","DOI":"10.1073\/pnas.0811261106","article-title":"The regulatory role of cell mechanics for migration of differentiating myeloid cells","volume":"106","author":"Paschke","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Biosensors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6374\/16\/9\/461\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T04:24:26Z","timestamp":1787804666000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6374\/16\/9\/461"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,25]]},"references-count":29,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["bios16090461"],"URL":"https:\/\/doi.org\/10.3390\/bios16090461","relation":{},"ISSN":["2079-6374"],"issn-type":[{"value":"2079-6374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,25]]}}}