• Open Access

Ultrasensitivity of Cell Adhesion to the Presence of Mechanically Strong Ligands

Mehdi Roein-Peikar, Qian Xu, Xuefeng Wang, and Taekjip Ha
Phys. Rev. X 6, 011001 – Published 5 January 2016

Abstract

Integrins, a class of membrane proteins involved in cell adhesion, participate in the cell’s sensing of the mechanical environments. We previously showed that, for the initial cell adhesion to occur, single integrins need to experience a threshold force of 40 pico-Newton (pN) through their bond with surface-bound ligands. This force requirement was determined using a series of double-stranded DNA tethers called tension gauge tethers (TGTs), each with a different rupture force, linked to the ligand. Here, we performed cell-adhesion experiments using surfaces coated with two different TGTs, one of a strong rupture force (around 54 pN) and the other of a weak rupture force (around 12 pN). When presented with one type of TGT only, cells adhered to the strong TGT-coated surface but not to the weak TGT-coated surface. However, when presented with both, the presence of the strong TGTs transforms the way cells respond to the weak TGTs such that cells treat both TGTs the same, as if the weak TGTs were strong. Furthermore, a subpopulation of cells can adhere to and spread on a surface displaying just a few molecules of the strong TGTs per cell if, and only if, they are presented along with many weak TGTs. This ultrasensitivity to just a few tethers that can withstand strong forces raises a question of how the cells can achieve such remarkable sensitivity to their mechanical environment without amplifying noise.

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  • Received 8 October 2014

DOI:https://doi.org/10.1103/PhysRevX.6.011001

This article is available under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.

Published by the American Physical Society

Authors & Affiliations

Mehdi Roein-Peikar1, Qian Xu2,3, Xuefeng Wang1,2, and Taekjip Ha1,2,3,4

  • 1Department of Physics and Center for the Physics of Living Cells, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA
  • 2Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA
  • 3Howard Hughes Medical Institute, Urbana, Illinois 61801, USA
  • 4Department of Biophysics and Biophysical Chemistry, Department of Biophysics and Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21205, USA

  • Corresponding author. tjha@jhu.edu

Popular Summary

The mechanical environment of human cells determines their properties. For example, stem cells change into bone cells if their environment is stiff, and stem cells change into fat cells if their environment is soft. Cells sense their immediate mechanical environments by making contact with nearby surfaces using thousands of mechanical contacts with proteins on their membranes. If the individual contacts can be easily broken, the cells do not adhere; cells adhere to the surrounding surface only if the mechanical contacts are strong. In this study, we find that certain types of cells can adhere to surfaces with weak contacts when there are only a few strong contacts per cell. In other words, an ultrasensitive cell is able to change its behavior even when only a few molecules on its surface experience strong mechanical tugging.

The strong and weak contacts in our study are made between integrin, a cell membrane receptor protein, and its ligand linked to surface-tethered double-stranded DNA with high and low rupture forces (54 and 12 pN, respectively). We label strong and weak with different colors, and we use both live and fixed cells in our experiments; each cell sits on top of 200,000 tethered molecules. Measurables include the degree of rupture and its spatial distribution. We show that, on average, two strong DNA tethers are sufficient to allow cells to adhere and spread if and only if there are thousands of weak tethers also present. We additionally discover that the presence of strong and weak tethers together results in cells responding to both tethers in the same way.

Our findings increase our understanding of cell adhesion, which is involved in many processes in the body, ranging from cancer metastasis to wound healing. We anticipate that future studies will reveal the molecular mechanisms of how cells integrate disparate signals from single molecular mechanical sensors to initiate their spreading response.

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Vol. 6, Iss. 1 — January - March 2016

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