The Biomechanics of Drug-Treated Leukemia Cells Investigated Using Optical Tweezers

Abstract

Leukemia is a very common cancer worldwide, and different drugs have been applied to treat the disease. However, the influence of the drugs on the biomechanical properties of leukemia cells, which are related to the risk of leukostasis, is still unknown. Moreover, accurate measurement of biomechanical properties of leukemia cells is still a challenging task because of their non-adherent nature and high sensitivity to the surrounding physiological conditions. In this study, a protocol to measure the biomechanical properties of leukemia cells by performing indentation tests using optical tweezers is proposed. The biomechanical properties of normal leukemia cells and cells treated with various cancer drugs, including phorbol 12-myristate 13-acetate (PMA), all-trans retinoic acid (ATRa), Cytoxan (CTX), and Dexamethasone (DEX), were measured. The adhesion between the cells and certain proteins existing in the extracellular matrix, i.e., fibronetin and collagen I, was also characterized with the help of a static adhesion assay. It was found that after treatment by ATRa, CTX, and DEX, the cells became softer, and the adhesion between the cells and the proteins became weaker. PMA treatment caused no change in the stiffness of the HL60 cells, but increased the stiffness of the K562 cells, and increased the cell–protein adhesion of both K562 cells and HL60 cells.

Microconstriction Arrays for High-Throughput Quantitative Measurements of Cell Mechanical Properties

“…Mechanical properties of K562 cells have been previously measured using different techniques. Indentation of optically trapped beads into cells immobilized on a fibronectin-coated glass surface gave a stiffness of 160 Pa (48). AFM measurements of cells trapped in microwells gave stiffness values at~50 Pa (11).…”

Accurate measurement of stiffness of leukemia cells and leukocytes using an optical trap by a rate-jump method

“…Some cells such as K562, macrophage and/or certain granulocytes do not even need such protein fixing. We have shown that optical tweezers can be used to perform indentation on these cells 20 .…”

“…In this paper, we demonstrate that the intrinsic elastic moduli of living cells can be extracted by using optical tweezers based on the rate-jump method. In contrast with other methods including atomic force microscopy (AFM), micropipette aspiration and magnetic tweezers, carrying out lateral indentation in an optical tweezers has the merit of allowing the indentation processing to be recorded, thus offering control of the indenter sphere at the desired indentation position with submicron precision [20][21][22] .…”

“…The crux of the controversy has been the large scatter often seen in the reported values of cell stiffness 23 , and such scatter is primarily due to the viscous effects of the cell structures and variations in the cell geometry, both of which are factors that can significantly affect the elastic modulus measurement 4,12,24 . On the other hand, reliable measurement of cell stiffness may be helpful in offering quantitative information for certain diseases 1, 20,[25][26][27][28] . In this report, the myelogenous leukemia cell line K562 29 was used as a prototype sample for lateral indentation experiments by polystyrene microspheres trapped by optical tweezers, with a purpose to evaluate the advantage of using the rate-jump protocol over the commonly used Hertzian method 30 .…”

Frequency‐dependent cell death by optical tweezers manipulation

“…Such stimuli are indeed commonly encountered in daily life, including mechanical vibrations, temperature fluctuations, and environmental radiations. Optical tweezers are commonly used to manipulate transparent microbeads to interact with cells (Liang et al, 1996), bacteria (Rasmussen et al, 2008), DNA (Zhuang, 2004), and RNA (Wen et al, 2007), to measure macromolecular interactions (Zhou et al, 2012), to do cell indentation (Zhou et al, 2011), and so forth. In the current study, optical tweezers were used to manipulate single cells mechanically at different frequencies and amplitudes, and their effects on the cells were observed with in situ optical and fluorescent microscopy.…”