Cell spheroid viscoelasticity is deformation-dependent

Scientific Reports, vol. 14, pp. 20013

Abstract

Tissue surface tension influences cell sorting and tissue fusion. Earlier mechanical studies suggest that multicellular spheroids actively reinforce their surface tension with applied force. Here we study this open question through high-throughput microfluidic micropipette aspiration measurements on cell spheroids to identify the role of force duration and spheroid deformability. In particular, we aspirate spheroid protrusions of mice fibroblast NIH3T3 and human embryonic HEK293T homogeneous cell spheroids into micron-sized capillaries for different pressures and monitor their viscoelastic creep behavior. We find that larger spheroid deformations lead to faster cellular retraction once the pressure is released, regardless of the applied force. Additionally, less deformable NIH3T3 cell spheroids with an increased expression level of alpha-smooth muscle actin, a cytoskeletal protein upregulating cellular contractility, also demonstrate slower cellular retraction after pressure release for smaller spheroid deformations. Moreover, HEK293T cell spheroids only display cellular retraction at larger pressures with larger spheroid deformations, despite an additional increase in viscosity at these larger pressures. These new insights demonstrate that spheroid viscoelasticity is deformation-dependent and challenge whether surface tension truly reinforces at larger aspiration pressures.

Authors 7

1. Ruben C. Boot

   Delft University of Technology

   Affiliation as printed

   Department of Chemical Engineering, Delft University of Technology, Delft, 2629, HZ, The Netherlands

2. Anouk van der Net

   Delft University of Technology

   Affiliation as printed

   Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, 2629, HZ, The Netherlands

3. Christos Gogou

   Delft University of Technology

   Affiliation as printed

   Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, 2629, HZ, The Netherlands

4. Pranav Mehta Aachen Department of Cell and Chemical Biology and Oncode Institute

   Leiden University Medical Center · Delft University of Technology

   Affiliation as printed

   Department of Cell and Chemical Biology and Oncode Institute, Leiden University Medical Center, Leiden, 2333, ZA, The Netherlands

   Department of Chemical Engineering, Delft University of Technology, Delft, 2629, HZ, The Netherlands

5. Dimphna H. Meijer

   Delft University of Technology

   Affiliation as printed

   Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, 2629, HZ, The Netherlands

6. Gijsje Hendrika Koenderink

   Delft University of Technology

   Affiliation as printed

   Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, 2629, HZ, The Netherlands

7. Pouyan E. Boukany corresponding

   Delft University of Technology

   Affiliation as printed

   Department of Chemical Engineering, Delft University of Technology, Delft, 2629, HZ, The Netherlands. p.e.boukany@tudelft.nl

   Department of Chemical Engineering, Delft University of Technology, Delft, 2629, HZ, The Netherlands