Investigating the Influence of Anti-Cancer Drugs on the Mechanics of Cells Using AFM

Abstract

The cytoskeleton comprises microtubules, actin microfilaments, and intermediate filaments. The cytoskeleton plays a role in the mechanical function of cell adhesion, motility, and migration. Currently, cancer cell mechanics is an important topic of understanding cancer progression. Atomic force microscopy (AFM) is one of the techniques used to determine the mechanical properties of cells. In this study, AFM was used to measure the force curves of U937 cancer cells treated with two types of anticancer drugs (colchicine and taxol), and alterations in the Young's modulus were subsequently investigated. The study results indicate that the force curve trend was dissimilar among the three types of cells (cells in the control group and in two types of anticancer drugs). In addition, when using the AFM to analyze the influence of drugs on the mechanical properties of cells, applying a small loading force from the AFM tip (small cell indentation depth) produced more accurate results. At a small cell indentation depth, the Young's modulus order was E colchicine <E control <E taxol because colchicine caused the cell microtubules to disassemble, thereby reducing cell strength, whereas taxol caused the microtubules to assemble, which increased cell strength. At a large cell indentation depth, the E colchicine value was the largest because colchicine reduced the strength and height of the cells and the effect of the underlying substrate was reflected in and influenced the force curve.

Nanomechanics in Monitoring the Effectiveness of Drugs Targeting the Cancer Cell Cytoskeleton

“…Taxanes and vinca alkaloids are not the only pair of microtubule-targeted agents studied. The other combinations employed are taxol/colchicine [ 70 ] or paclitaxel/S-HM -3 (a tumor angiogenesis inhibitor with a short half-life) [ 71 ]. Analogously to vincristine, colchicine destabilizes microtubules.…”

Microtubule disruption changes endothelial cell mechanics and adhesion

“…were one of the first groups to study this behavior extensively, stating that cell mechanics (in their case Young’s Modulus) mostly depends on the actin filaments while microtubules play only a minor role 7 . More recently, different works have underlined the role of microtubules in cell mechanics 8,9 . Microtubules play a prominent role in mitosis, intracellular transport, the formation of cilia and flagella, developmental biology, focal adhesion formation, and many other processes 10 .…”

Studying nucleic envelope and plasma membrane mechanics of eukaryotic cells using confocal reflectance interferometric microscopy

“…The mechanical environment plays important role in many cellular physiological and pathological processes 1 . The impact of drug response on cellular biomechanics has also been highlighted as an important consideration in mechanopharmacology 2–4 . Atomic force microscopy (AFM) 5 and optical tweezers-based methods 6 can provide direct measurement of the cellular plasma membrane elasticity.…”