Elastic properties of leukemic cells linked to maturation stage and integrin activation

Ceri J. Richards; Albertus T.J. Wierenga; Annet Z. Brouwers-Vos; Emmanouil Kyrloglou; Laura S. Dillingh; Patty P.M.F.A. Mulder; Georgios Palasantzas; Jan Jacob Schuringa; Wouter H. Roos

doi:10.1016/j.isci.2025.112150

Elastic properties of leukemic cells linked to maturation stage and integrin activation

Ceri J. Richards
, Albertus T.J. Wierenga
, Annet Z. Brouwers-Vos
, Emmanouil Kyrloglou
, Laura S. Dillingh
, Patty P.M.F.A. Mulder
, Georgios Palasantzas
, Jan Jacob Schuringa
, Wouter H. Roos

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Acute myeloid leukemia (AML) remains challenging to cure. In addition to mutations that alter cell functioning, biophysical properties are modulated by external cues. In particular, membrane proteins that interact with the bone marrow niche can induce cellular changes. Here, we develop an atomic force microscopy (AFM) approach to measure non-adherent AML cell mechanical properties. The Young's modulus of the AML cell line, THP-1, increased in response to retronectin, whereas knock-out of the adhesion protein ITGB1 resulted in no response to retronectin. Confocal microscopy revealed different actin cytoskeleton morphologies for wild-type and ITGB1 knock-out cells exposed to retronectin. These results indicate that ITGB1 mediates stimuli-induced cellular mechanoresponses through cytoskeletal changes. We next used AFM to investigate the elastic properties of primary AML cells and found that more committed cells had lower Young's moduli than immature AMLs. Overall, this provides a platform for investigating the molecular mechanisms involved in leukemic cell mechanoresponse.

Original language	English
Article number	112150
Journal	iScience
Volume	28
Issue number	4
DOIs	https://doi.org/10.1016/j.isci.2025.112150
Publication status	Published - 18 Apr 2025
Externally published	Yes

Funding

This work is supported by a Dieptestrategie grant of the Zernike Institute National Research Centre of the Rijksuniversiteit Groningen . We thank the Flow Cytometry Unit of the University Medical Center, Groningen. Moreover, we thank P. de Haan, and E. Verpoorte of the Pharmaceutical Analysis group, Groningen Research Institute of Pharmacy for the providing the photolithography mask used for the PFPE wells. We also thank G. Wlodarczyk-Biegun for providing the phalloidin.

Funders
Zernike Institute National Research Centre of the Rijksuniversiteit Groningen

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@article{03b472d63f124583982357b293c8b55f,

title = "Elastic properties of leukemic cells linked to maturation stage and integrin activation",

abstract = "Acute myeloid leukemia (AML) remains challenging to cure. In addition to mutations that alter cell functioning, biophysical properties are modulated by external cues. In particular, membrane proteins that interact with the bone marrow niche can induce cellular changes. Here, we develop an atomic force microscopy (AFM) approach to measure non-adherent AML cell mechanical properties. The Young's modulus of the AML cell line, THP-1, increased in response to retronectin, whereas knock-out of the adhesion protein ITGB1 resulted in no response to retronectin. Confocal microscopy revealed different actin cytoskeleton morphologies for wild-type and ITGB1 knock-out cells exposed to retronectin. These results indicate that ITGB1 mediates stimuli-induced cellular mechanoresponses through cytoskeletal changes. We next used AFM to investigate the elastic properties of primary AML cells and found that more committed cells had lower Young's moduli than immature AMLs. Overall, this provides a platform for investigating the molecular mechanisms involved in leukemic cell mechanoresponse.",

author = "Richards, \{Ceri J.\} and Wierenga, \{Albertus T.J.\} and Brouwers-Vos, \{Annet Z.\} and Emmanouil Kyrloglou and Dillingh, \{Laura S.\} and Mulder, \{Patty P.M.F.A.\} and Georgios Palasantzas and Schuringa, \{Jan Jacob\} and Roos, \{Wouter H.\}",

year = "2025",

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doi = "10.1016/j.isci.2025.112150",

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AU - Richards, Ceri J.

AU - Wierenga, Albertus T.J.

AU - Brouwers-Vos, Annet Z.

AU - Kyrloglou, Emmanouil

AU - Dillingh, Laura S.

AU - Mulder, Patty P.M.F.A.

AU - Palasantzas, Georgios

AU - Schuringa, Jan Jacob

AU - Roos, Wouter H.

PY - 2025/4/18

Y1 - 2025/4/18

N2 - Acute myeloid leukemia (AML) remains challenging to cure. In addition to mutations that alter cell functioning, biophysical properties are modulated by external cues. In particular, membrane proteins that interact with the bone marrow niche can induce cellular changes. Here, we develop an atomic force microscopy (AFM) approach to measure non-adherent AML cell mechanical properties. The Young's modulus of the AML cell line, THP-1, increased in response to retronectin, whereas knock-out of the adhesion protein ITGB1 resulted in no response to retronectin. Confocal microscopy revealed different actin cytoskeleton morphologies for wild-type and ITGB1 knock-out cells exposed to retronectin. These results indicate that ITGB1 mediates stimuli-induced cellular mechanoresponses through cytoskeletal changes. We next used AFM to investigate the elastic properties of primary AML cells and found that more committed cells had lower Young's moduli than immature AMLs. Overall, this provides a platform for investigating the molecular mechanisms involved in leukemic cell mechanoresponse.

AB - Acute myeloid leukemia (AML) remains challenging to cure. In addition to mutations that alter cell functioning, biophysical properties are modulated by external cues. In particular, membrane proteins that interact with the bone marrow niche can induce cellular changes. Here, we develop an atomic force microscopy (AFM) approach to measure non-adherent AML cell mechanical properties. The Young's modulus of the AML cell line, THP-1, increased in response to retronectin, whereas knock-out of the adhesion protein ITGB1 resulted in no response to retronectin. Confocal microscopy revealed different actin cytoskeleton morphologies for wild-type and ITGB1 knock-out cells exposed to retronectin. These results indicate that ITGB1 mediates stimuli-induced cellular mechanoresponses through cytoskeletal changes. We next used AFM to investigate the elastic properties of primary AML cells and found that more committed cells had lower Young's moduli than immature AMLs. Overall, this provides a platform for investigating the molecular mechanisms involved in leukemic cell mechanoresponse.

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DO - 10.1016/j.isci.2025.112150

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VL - 28

JO - iScience

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ER -

Elastic properties of leukemic cells linked to maturation stage and integrin activation

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