Surface attachment of protein fibrils via covalent modification strategies.

Chemical control of surface functionality and topography is an essential requirement for many technological purposes. In particular, the covalent attachment of monomeric proteins to surfaces has been the object of intense studies in recent years, for applications as varied as electrochemistry, immuno-sensing, and the production of biocompatible coatings. Little is known, however, about the characteristics and requirements underlying surface attachment of supramolecular protein nanostructures. Amyloid fibrils formed by the self-assembly of peptide and protein molecules represent one important class of such structures. These highly organized beta-sheet-rich assemblies are a hallmark of a range of neurodegenerative disorders, including Alzheimer's disease and type II diabetes, but recent findings suggest that they have much broader significance, potentially representing the global free energy minima of the energy landscapes of proteins and having potential applications in material science. In this paper, we describe strategies for attaching amyloid fibrils formed from different proteins to gold surfaces under different solution conditions. Our methods involve the reaction of sulfur containing small molecules (cystamine and 2-iminothiolane) with the amyloid fibrils, enabling their covalent linkage to gold surfaces. We demonstrate that irreversible attachment using these approaches makes possible quantitative analysis of experiments using biosensor techniques, such as quartz crystal microbalance (QCM) assays that are revolutionizing our understanding of the mechanisms of amyloid growth and the factors that determine its kinetic behavior. Moreover, our results shed light on the nature and relative importance of covalent versus noncovalent forces acting on protein superstructures at metal surfaces.

Specificity of reflex adaptation for task-relevant variability.

The motor system responds to perturbations with reflexes, such as the vestibulo-ocular reflex or stretch reflex, whose gains adapt in response to novel and fixed changes in the environment, such as magnifying spectacles or standing on a tilting platform. Here we demonstrate a reflex response to shifts in the hand's visual location during reaching, which occurs before the onset of voluntary reaction time, and investigate how its magnitude depends on statistical properties of the environment. We examine the change in reflex response to two different distributions of visuomotor discrepancies, both of which have zero mean and equal variance across trials. Critically one distribution is task relevant and the other task irrelevant. The task-relevant discrepancies are maintained to the end of the movement, whereas the task-irrelevant discrepancies are transient such that no discrepancy exists at the end of the movement. The reflex magnitude was assessed using identical probe trials under both distributions. We find opposite directions of adaptation of the reflex response under these two distributions, with increased reflex magnitudes for task-relevant variability and decreased reflex magnitudes for task-irrelevant variability. This demonstrates modulation of reflex magnitudes in the absence of a fixed change in the environment, and shows that reflexes are sensitive to the statistics of tasks with modulation depending on whether the variability is task relevant or task irrelevant.