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The Viscoelasticity of Membrane Tethers and Its Importance for Cell Adhesion

Applied Physics and Biophysics, Ludwig-Maximilians University, 80799 Munich, Germany

Correspondence: Address reprint requests to Kay-Eberhard Gottschalk, Tel.: 49-89-2180-3436; Fax: 49-89-2180-2050; E-mail: kay.gottschalk{at}physik.uni-muenchen.de.

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 such as 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 dependent not only 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 k_t = 1.6 µN/m, an initial membrane rigidity of k_i = 260 µN/m, and a viscosity of µ = 5.9 µN·s/m. Integrins exist in different activation states. When activating the integrin with Mg²⁺, we observe altered viscoelastic parameters of k_t = 0.9 µN/m, k_i = 190 µN/m, and µ = 6.0 µ N·s/m. Based on our model, we postulate that anchorage-related effects are common regulating mechanisms for cellular adhesion beyond affinity regulation.