Title :
Quantitative Analysis of Drug-Induced Complement-Mediated Cytotoxic Effect on Single Tumor Cells Using Atomic Force Microscopy and Fluorescence Microscopy
Author :
Mi Li ; Lianqing Liu ; Ning Xi ; Yuechao Wang ; Xiubin Xiao ; Weijing Zhang
Author_Institution :
State Key Lab. of Robot., Shenyang Inst. of Autom., Shenyang, China
Abstract :
In the antibody-based targeted therapies of B-cell lymphomas, complement-mediated cytotoxicity (CMC) is an important mechanism. CMC is activated after the binding of drugs (monoclonal antibodies) to tumor cells. The activation of CMC ultimately leads to the lysis of tumor cells. However, it remains poorly understood how CMC alters the morphology and mechanics of single tumor cells at the nanoscale. In recent years, nanoscopic observations of cellular behaviors with the use of atomic force microscopy (AFM) have contributed much to the field of cell biology. In this work, by combining AFM with fluorescence microscopy, the detailed changes in cellular ultra-microstructures and mechanical properties during the process of CMC were quantitatively investigated on single tumor cells. AFM imaging distinctly showed that the CMC effect could lead to the formation of nano holes on the tumor cells. Quantitative analysis of AFM images indicated that cell surface became lower and rougher after the CMC process. The cellular mechanics measurements showed that during the process of CMC cells firstly softened and finally stiffened, which was validated by dynamically monitoring the mechanical changes of single living cells during CMC. The experimental results provide novel insights into the antibody-dependent CMC.
Keywords :
atomic force microscopy; biomechanics; blood; cancer; cellular biophysics; chemical analysis; drugs; fluorescence; optical microscopy; tumours; AFM image quantitative analysis; AFM imaging; AFM-fluorescence microscopy combination; B-cell lymphomas; CMC activation; CMC effect; CMC process; antibody-based targeted therapies; antibody-dependent CMC; atomic force microscopy; cell surface; cellular behavior nanoscopic observations; cellular ultramicrostructures; complement-mediated cytotoxicity; drug binding; drug-induced complement-mediated cytotoxic effect; monoclonal antibodies; nanohole formation; single living cell mechanical changes; single tumor cell mechanics; single tumor cell morphology; tumor cell lysis; Computer architecture; Fluorescence; Force; Microprocessors; Rough surfaces; Surface morphology; Surface roughness; Antibody; atomic force microscopy; cell; complement- mediated cytotoxicity; lymphoma; mechanical properties;
Journal_Title :
NanoBioscience, IEEE Transactions on
DOI :
10.1109/TNB.2014.2370759