Kubiak Andrzej, Chighizola Matteo, Schulte Carsten, Bryniarska Natalia, Wesołowska Julita, Pudełek Maciej, Lasota Małgorzata, Ryszawy Damian, Basta-Kaim Agnieszka, Laidler Piotr, Podestà Alessandro, Lekka Małgorzata
Department of Biophysical Microstructures, Institute of Nuclear Physics, Polish Academy of Sciences, PL-31342 Kraków, Poland.
Nanoscale. 2021 Mar 28;13(12):6212-6226. doi: 10.1039/d0nr06464e. Epub 2021 Mar 19.
The crucial role of microtubules in the mitotic-related segregation of chromosomes makes them an excellent target for anticancer microtubule targeting drugs (MTDs) such as vinflunine (VFL), colchicine (COL), and docetaxel (DTX). MTDs affect mitosis by directly perturbing the structural organisation of microtubules. By a direct assessment of the biomechanical properties of prostate cancer DU145 cells exposed to different MTDs using atomic force microscopy, we show that cell stiffening is a response to the application of all the studied MTDs (VFL, COL, DTX). Changes in cellular rigidity are typically attributed to remodelling of the actin filaments in the cytoskeleton. Here, we demonstrate that cell stiffening can be driven by crosstalk between actin filaments and microtubules in MTD-treated cells. Our findings improve the interpretation of biomechanical data obtained for living cells in studies of various physiological and pathological processes.
微管在有丝分裂相关的染色体分离中起着关键作用，这使得它们成为抗癌微管靶向药物（MTDs）的理想靶点，如长春氟宁（VFL）、秋水仙碱（COL）和多西他赛（DTX）。MTDs通过直接扰乱微管的结构组织来影响有丝分裂。通过使用原子力显微镜直接评估暴露于不同MTDs的前列腺癌DU145细胞的生物力学特性，我们发现细胞变硬乃是对所有研究的MTDs（VFL、COL、DTX）作用的一种反应。细胞刚性的变化通常归因于细胞骨架中肌动蛋白丝的重塑。在此，我们证明在MTD处理的细胞中，细胞变硬可由肌动蛋白丝与微管之间的相互作用驱动。我们的研究结果改进了在各种生理和病理过程研究中对活细胞获得的生物力学数据的解释。
