The Visocelasticity of Membrane Tethers and its Importance for Cell Adhesion
Julia Schmitz 1, Benoit Martin 1 and Kay Eberhard Gottschalk 2*
1 LMU
2 Ludwig-Maximilians University
* To whom correspondence should be addressed. E-mail: kay.gottschalk{at}physik.uni-muenchen.de.
Submitted on October 22, 2007
Revised on December 4, 2007
Accepted on 28 March 2008
 |
Abstract |
|---|
Cell adhesion mechanically couples cells to surfaces. The durability of individual bonds between the adhesive receptors and their ligands in the presence of forces determines the cellular adhesion strength. For adhesive receptors like integrins, it is a common paradigm that the cell regulates its adhesion strength by altering the affinity state of the receptors. However, the probability distribution of rupture forces is not only dependent on the affinity of individual receptor-ligand bonds, but also on the mechanical compliance of the cellular anchorage of the receptor. Hence, by altering the anchorage, the cell can regulate its adhesion strength without changing the affinity of the receptor. Here, we analyze the anchorage of the integrin VLA-4 with its ligand VCAM-1. For this purpose, we develop a model based on the Kelvin body, which allows one to quantify the mechanical properties of the adhesive receptor's anchorage using atomic force microscopy on living cells. As we demonstrate, the measured force curves give valuable insight into the mechanics of the cellular anchorage of the receptor, which is described by the tether-stiffness, the membrane rigidity and the membrane viscosity. The measurements relate to a tether stiffness of kt=1.6µN/m, an initial membrane rigidity of ki=260µN/m and a viscosity of µ=5.9µN·s/m. Integrins exist in different activation states. When activating the integrin with Mg2+, we observe altered viscoelastic parameters of kt=0.9µN/m, ki=190µN/m and µ=6.0µN·s/m. Based on our model, we postulate that anchorage-related effects are common regulating mechanisms for cellular adhesion beyond affinity regulation.
Key Words:
AFM, Kelvin-body, cell mechanics, integrin, nano-environment, viscoelasticity
