The viscoelasticity of membrane tethers and its importance for cell adhesion

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 mu N/m, an initial membrane rigidity of k(i)=260 mu N/m, and a viscosity of mu=5.9 mu N.s/m. Integrins exist in different activation states. When activating the integrin with Mg2+, we observe altered viscoelastic parameters of k(t)=0.9 mu N/m, k(i)=190 mu N/m, and mu=6.0 mu N.s/m. Based on our model, we postulate that anchorage-related effects are common regulating mechanisms for cellular adhesion beyond affinity regulation.