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

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-03-04 DOI:10.1016/j.isci.2025.112150

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

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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.

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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