Richards Ceri J, Wierenga Albertus T J, Brouwers-Vos Annet Z, Kyrloglou Emmanouil, Dillingh Laura S, Mulder Patty P M F A, Palasantzas Georgios, Schuringa Jan Jacob, Roos Wouter H
Moleculaire Biofysica, Zernike Instituut, Rijksuniversiteit Groningen, 9747 AG Groningen, the Netherlands.
Department of Experimental Hematology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, the Netherlands.
iScience. 2025 Mar 4;28(4):112150. doi: 10.1016/j.isci.2025.112150. eCollection 2025 Apr 18.
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 resulted in no response to retronectin. Confocal microscopy revealed different actin cytoskeleton morphologies for wild-type and knock-out cells exposed to retronectin. These results indicate that 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.
急性髓系白血病（AML）的治愈仍然具有挑战性。除了改变细胞功能的突变外，生物物理特性还受外部线索调节。特别是，与骨髓生态位相互作用的膜蛋白可诱导细胞变化。在此，我们开发了一种原子力显微镜（AFM）方法来测量非贴壁AML细胞的力学特性。AML细胞系THP-1的杨氏模量在纤连蛋白作用下增加，而粘附蛋白敲除导致对纤连蛋白无反应。共聚焦显微镜显示，暴露于纤连蛋白的野生型和敲除细胞具有不同的肌动蛋白细胞骨架形态。这些结果表明， 通过细胞骨架变化介导刺激诱导的细胞机械反应。接下来，我们使用AFM研究原发性AML细胞的弹性特性，发现分化程度更高的细胞比未成熟AML细胞的杨氏模量更低。总体而言，这为研究白血病细胞机械反应所涉及的分子机制提供了一个平台。
