期刊
BIOMATERIALS
卷 177, 期 -, 页码 113-124出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2018.05.058
关键词
Cancer; Microenvironment; Viscosity; Mechanotransduction; Migration
资金
- The Liver Group Charity, United Kingdom
- Marie Curie CIG, United Kingdom [PCIG14-GA-2013-631011]
- BBSRC, United Kingdom [BB/P006108/1]
- Chinese Scholarship Council, China
- The Liver Group Charity
- BBSRC [BB/P006108/1] Funding Source: UKRI
The extracellular fluid (ECF) is a crowded environment containing macromolecules that determine its characteristic density, osmotic pressure, and viscosity, which greatly differ between tissues. Precursors and products of degradation of biomaterials enhance ECF crowding and often increase its viscosity. Also, increases in ECF viscosity are related to mucin-producing adenocarcinomas. However, the effect of ECF viscosity on cells remains largely unexplored. Here we show that viscosity-enhancing polymer solutions promote mesenchymal-like cell migration in liver cancer cell lines. Also, we demonstrate that viscosity enhances integrin-dependent cell spreading rate and causes actin cytoskeleton re-arrangements leading to larger cell area, nuclear flattening, and nuclear translocation of YAP and beta-catenin, proteins involved in mechanotransduction. Finally, we describe a relationship between ECF viscosity and substrate stiffness in determining cell area, traction force generation and mechanotransduction, effects that are actin-dependent only on <= 40 kPa substrates. These findings reveal that enhancing ECF viscosity can induce major biological responses including cell migration and substrate mechanosensing. (C) 2018 Elsevier Ltd. All rights reserved.
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