Interactions of proteins with inorganic surfaces are of high importance in biological events and in modern biotechnological applications. Therefore, peptides have been engineered to recognize inorganic surfaces with high specificity. However, the underlying interactions are still not well understood. Here, we investigated the adsorption of amino acids as protein building blocks onto a Au(111) surface. In particular, using molecular dynamics simulations, we calculated the potential of mean force between all the 20 amino acids and the gold surface. We found a strong dependence of the binding affinities on the chemical character of the amino acids. Additionally, the interaction free energy is correlated with the propensity of amino acids to form beta-sheets, hinting at design principles for gold binding peptides and induction of beta-sheet formation near surfaces.

Amyotrophic lateral sclerosis (ALS) is a devastating progressive neurodegenerative disease affecting primarily the upper and lower motor neurons. A common feature of all ALS cases is a well-characterized neuroinflammatory reaction within the central nervous system (CNS). However, much less is known about the role of the peripheral immune system and its interplay with CNS resident immune cells in motor neuron degeneration. Here, we characterized peripheral monocytes in both temporal and spatial dimensions of ALS pathogenesis. We found the circulating monocytes to be deregulated in ALS regarding subtype constitution, function and gene expression. Moreover, we show that CNS infiltration of peripheral monocytes correlates with improved motor neuron survival in a genetic ALS mouse model. Furthermore, application of human immunoglobulins or fusion proteins containing only the human Fc, but not the Fab antibody fragment, increased CNS invasion of peripheral monocytes and delayed the disease onset. Our results underline the importance of peripheral monocytes in ALS pathogenesis and are in agreement with a protective role of monocytes in the early phase of the disease. The possibility to boost this beneficial function of peripheral monocytes by application of human immunoglobulins should be evaluated in clinical trials.

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 microN/m, an initial membrane rigidity of k(i) = 260 microN/m, and a viscosity of mu = 5.9 microN x s/m. Integrins exist in different activation states. When activating the integrin with Mg(2+), we observe altered viscoelastic parameters of k(t) = 0.9 microN/m, k(i) = 190 microN/m, and mu = 6.0 microN x s/m. Based on our model, we postulate that anchorage-related effects are common regulating mechanisms for cellular adhesion beyond affinity regulation.

The interactions of amino acids with inorganic surfaces are of interest for biologists and biotechnologists alike. However, the structural determinants of peptide-surface interactions have remained elusive, but are important for a structural understanding of the interactions of biomolecules with gold surfaces. Molecular dynamics simulations are a tool to analyze structures of amino acids on surfaces. However, such an approach is challenging due to lacking parameterization for many surfaces and the polarizability of metal surfaces. Herein, we report DFT calculations of amino acid fragments in vacuo and molecular dynamics simulations of the interaction of all amino acids with a gold(111) surface in explicit solvent, using the recently introduced polarizable gold force field GolP. We describe preferred orientations of the amino acids on the metal surface. We find that all amino acids preferably interact with the gold surface at least partially with their backbone, underlining an unfolding propensity of gold surfaces.