Nucleus of Circulating Tumor Cell Determines Its Translocation Through Biomimetic Microconstrictions and Its Physical Enrichment by Microfiltration.

Autor: Xia Y; Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, 16802, USA., Wan Y; Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, 16802, USA., Hao S; Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, 16802, USA., Nisic M; The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA., Harouaka RA; Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, 16802, USA., Chen Y; Department of Electrical Engineering, The Pennsylvania State University, University Park, PA, 16802, USA., Zou X; Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, 16802, USA., Zheng SY; Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, 16802, USA.; The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.; Department of Electrical Engineering, The Pennsylvania State University, University Park, PA, 16802, USA.; Penn State Materials Research Institute, The Pennsylvania State University, University Park, PA, 16802, USA.; Penn State Cancer Institute, The Pennsylvania State University, University Park, PA, 16802, USA.
Jazyk: angličtina
Zdroj: Small (Weinheim an der Bergstrasse, Germany) [Small] 2018 Nov; Vol. 14 (44), pp. e1802899. Date of Electronic Publication: 2018 Oct 04.
DOI: 10.1002/smll.201802899
Abstrakt: The mechanism of cells passing through microconstrictions, such as capillaries and endothelial junctions, influences metastasis of circulating tumor cells (CTCs) in vivo, as well as size-based enrichment of CTCs in vitro. However, very few studies observe such translocation of microconstrictions in real time, and thus the inherent biophysical mechanism is poorly understood. In this study, a multiplexed microfluidic device is fabricated for real-time tracking of cell translocation under physiological pressure and recording deformation of the whole cell and nucleus, respectively. It is found that the deformability and size of the nucleus instead of the whole cell dominate cellular translocation through microconstrictions under a normal physiological pressure range. More specifically, cells with a large and stiff nucleus are prone to be blocked by relatively small constrictions. The same phenomenon is also observed in the size-based enrichment of CTCs from peripheral blood of metastatic cancer patients. These findings are different from a popular viewpoint that the size and deformability of a whole cell mainly determine cell translation through microconstrictions, and thus may elucidate interactions between CTCs and capillaries from a new perspective and guide the rational design of size-based microfilters for rare cell enrichment.
(© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE