Extracellular fluid viscosity enhances liver cancer cell mechanosensing and migration.

J. Gonzalez-Molina,Xiaoli Zhang,M. Borghesan,Joana Mendonça da Silva,Maooz Awan,B. Fuller,Núria Gavara,C. Selden

Published 2018 in Biomaterials

ABSTRACT

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 β-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.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-56 of 56 references · Page 1 of 1

CITED BY

Showing 1-100 of 105 citing papers · Page 1 of 2