Cortical stiffness of keratinocytes measured by lateral indentation with optical tweezers

PLoS One. 2020 Dec 31;15(12):e0231606. doi: 10.1371/journal.pone.0231606. eCollection 2020.

Abstract

Keratin intermediate filaments are the principal structural element of epithelial cells. Their importance in providing bulk cellular stiffness is well recognized, but their role in the mechanics of cell cortex is less understood. In this study, we therefore compared the cortical stiffness of three keratinocyte lines: primary wild type cells (NHEK2), immortalized wild type cells (NEB1) and immortalized mutant cells (KEB7). The cortical stiffness was measured by lateral indentation of cells with AOD-steered optical tweezers without employing any moving mechanical elements. The method was validated on fixed cells and Cytochalasin-D treated cells to ensure that the observed variations in stiffness within a single cell line were not a consequence of low measurement precision. The measurements of the cortical stiffness showed that primary wild type cells were significantly stiffer than immortalized wild type cells, which was also detected in previous studies of bulk elasticity. In addition, a small difference between the mutant and the wild type cells was detected, showing that mutation of keratin impacts also the cell cortex. Thus, our results indicate that the role of keratins in cortical stiffness is not negligible and call for further investigation of the mechanical interactions between keratins and elements of the cell cortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism*
  • Actin Cytoskeleton / ultrastructure
  • Cell Line
  • Cytochalasin D / pharmacology
  • Elasticity / drug effects
  • Gene Expression
  • Hardness / drug effects
  • Humans
  • Intermediate Filaments / metabolism*
  • Intermediate Filaments / ultrastructure
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism*
  • Keratinocytes / ultrastructure
  • Keratins / genetics
  • Keratins / metabolism*
  • Microtubules / metabolism*
  • Microtubules / ultrastructure
  • Optical Tweezers
  • Organ Specificity

Substances

  • Cytochalasin D
  • Keratins

Grants and funding

This work resulted from a collaboration initiated by the COST Action CA15214 (EuroCellNet). MG and RDMT thank the support of FEDER funds through the Operational Program Competitiveness Factors - COMPETE and by national funds by FCT - Foundation for Science and Technology under the strategic project UID/FIS/04564/2016 and under PTDC/BIA-CEL/31743/2017. MG thanks support by UE/FEDER funds through the program COMPETE 2020, under the project CENTRO-01-0145-FEDER-000014 (MATIS). RDMT acknowledges FCT’s support through the FCT Researcher Program. The work was also supported by Slovenian Research Agency Program Grants P1-0055 (JD, BS and SZJ)and P1-0390 (ML). This work was supported by the Republic of Slovenia Ministry of Education, Science and Sport and the EraCoSysMed (JTC-2 2017) "4D-HEALING" grant, and the Celsa Alliance grant to ML (prof Radovan Komel). None of the funders plaid any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.