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Nanomechanical measurement of adhesion and migration of leukemia cells with phorbol 12-myristate 13-acetate treatment

Authors Zhou ZL, Ma J, Tong MH, Chan BP, Wong AST, Ngan AHW

Received 25 July 2016

Accepted for publication 29 September 2016

Published 7 December 2016 Volume 2016:11 Pages 6533—6545

DOI https://doi.org/10.2147/IJN.S118065

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Thomas Webster


Zhuo Long Zhou,1 Jing Ma,2 Ming-Hui Tong,1 Barbara Pui Chan,1 Alice Sze Tsai Wong,2 Alfonso Hing Wan Ngan1

1Department of Mechanical Engineering, 2School of Biological Sciences, University of Hong Kong, Hong Kong, People’s Republic of China


Abstract: The adhesion and traction behavior of leukemia cells in their microenvironment is directly linked to their migration, which is a prime issue affecting the release of cancer cells from the bone marrow and hence metastasis. In assessing the effectiveness of phorbol 12-myristate 13-acetate (PMA) treatment, the conventional batch-cell transwell-migration assay may not indicate the intrinsic effect of the treatment on migration, since the treatment may also affect other cellular behavior, such as proliferation or death. In this study, the pN-level adhesion and traction forces between single leukemia cells and their microenvironment were directly measured using optical tweezers and traction-force microscopy. The effects of PMA on K562 and THP1 leukemia cells were studied, and the results showed that PMA treatment significantly increased cell adhesion with extracellular matrix proteins, bone marrow stromal cells, and human fibroblasts. PMA treatment also significantly increased the traction of THP1 cells on bovine serum albumin proteins, although the effect on K562 cells was insignificant. Western blots showed an increased expression of E-cadherin and vimentin proteins after the leukemia cells were treated with PMA. The study suggests that PMA upregulates adhesion and thus suppresses the migration of both K562 and THP1 cells in their microenvironment. The ability of optical tweezers and traction-force microscopy to measure directly pN-level cell–protein or cell–cell contact was also demonstrated.

Keywords: adhesion, migration, cell-to-cell contact, optical trapping, traction-force microscopy, protein micropillar matrix

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