216 research outputs found
Is adhesion superficial? Silicon wafers as a model system to study van der Waals interactions
Adhesion is a key issue for researchers of various fields, it is therefore of
uppermost importance to understand the parameters that are involved. Commonly,
only surface parameters are employed to determine the adhesive forces between
materials. Yet, van der Waals forces act not only between atoms in the vicinity
of the surface, but also between atoms in the bulk material. In this review, we
describe the principles of van der Waals interactions and outline experimental
and theoretical studies investigating the influence of the subsurface material
on adhesion. In addition, we present a collection of data indicating that
silicon wafers with native oxide layers are a good model substrate to study van
der Waals interactions with coated materials
Magneto-Optical Relaxation Measurements of Functionalized Nanoparticles as a Novel Biosensor
Measurements of magneto-optical relaxation signals of magnetic nanoparticles functionalized with biomolecules are a novel biosensing tool. Upon transmission of a laser beam through a nanoparticle suspension in a pulsed magnetic field, the properties of the laser beam change. This can be detected by optical methods. Biomolecular binding events leading to aggregation of nanoparticles are ascertainable by calculating the relaxation time and from this, the hydrodynamic diameters of the involved particles from the optical signal. Interaction between insulin-like growth factor 1 (IGF-1) and its antibody was utilized for demonstration of the measurement setup applicability as an immunoassay. Furthermore, a formerly developed kinetic model was utilized in order to determine kinetic parameters of the interaction. Beside utilization of the method as an immunoassay it can be applied for the characterization of diverse magnetic nanoparticles regarding their size and size distribution
Towards the clinical implementation of pharmacogenetics in bipolar disorder.
BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD
Adhesion of membranes via receptor-ligand complexes: Domain formation, binding cooperativity, and active processes
Cell membranes interact via anchored receptor and ligand molecules. Central
questions on cell adhesion concern the binding affinity of these
membrane-anchored molecules, the mechanisms leading to the receptor-ligand
domains observed during adhesion, and the role of cytoskeletal and other active
processes. In this review, these questions are addressed from a theoretical
perspective. We focus on models in which the membranes are described as elastic
sheets, and the receptors and ligands as anchored molecules. In these models,
the thermal membrane roughness on the nanometer scale leads to a cooperative
binding of anchored receptor and ligand molecules, since the receptor-ligand
binding smoothens out the membranes and facilitates the formation of additional
bonds. Patterns of receptor domains observed in Monte Carlo simulations point
towards a joint role of spontaneous and active processes in cell adhesion. The
interactions mediated by the receptors and ligand molecules can be
characterized by effective membrane adhesion potentials that depend on the
concentrations and binding energies of the molecules.Comment: Review article, 13 pages, 9 figures, to appear in Soft Matte
Vinculin potentiates E-cadherin mechanosensing and is recruited to actin-anchored sites within adherens junctions in a myosin IIâdependent manner
Vinculin localizes to tension-bearing cellâcell junctions to help transmit signals from E-cadherin to the actin cytoskeleton in response to mechanical stress
Real-time intermembrane force measurements and imaging of lipid domain morphology during hemifusion
Membrane fusion is the core process in membrane trafficking and is essential for cellular transport of proteins and other biomacromolecules. During protein-mediated membrane fusion, membrane proteins are often excluded from the membrane-membrane contact, indicating that local structural transformations in lipid domains play a major role. However, the rearrangements of lipid domains during fusion have not been thoroughly examined. Here using a newly developed Fluorescence Surface Forces Apparatus (FL-SFA), migration of liquid-disordered clusters and depletion of liquid-ordered domains at the membrane-membrane contact are imaged in real time during hemifusion of model lipid membranes, together with simultaneous force-distance and lipid membrane thickness measurements. The load and contact time-dependent hemifusion results show that the domain rearrangements decrease the energy barrier to fusion, illustrating the significance of dynamic domain transformations in membrane fusion processes. Importantly, the FL-SFA can unambiguously correlate interaction forces and in situ imaging in many dynamic interfacial systems.open0
Cadherin exits the junction by switching its adhesive bond
Intercellular traction forces or lateral alignment of cadherin molecules can influence adherens junction dynamics by altering the cadherin dimerization interface
An alternative pathway for alphavirus entry
The study of alphavirus entry has been complicated by an inability to clearly identify a receptor and by experiments which only tangentially and indirectly examine the process, producing results that are difficult to interpret. The mechanism of entry has been widely accepted to be by endocytosis followed by acidification of the endosome resulting in virus membrane-endosome membrane fusion. This mechanism has come under scrutiny as better purification protocols and improved methods of analysis have been brought to the study. Results have been obtained that suggest alphaviruses infect cells directly at the plasma membrane without the involvement of endocytosis, exposure to acid pH, or membrane fusion. In this review we compare the data which support the two models and make the case for an alternative pathway of entry by alphaviruses
Interatomic potentials and solvation parameters from protein engineering data for buried residues
Van der Waals (vdW) interaction energies between different atom types, energies of hydrogen bonds (Hâbonds), and atomic solvation parameters (ASPs) have been derived from the published thermodynamic stabilities of 106 mutants with available crystal structures by use of an originally designed model for the calculation of freeâenergy differences. The set of mutants included substitutions of uncharged, inflexible, waterâinaccessible residues in Îąâhelices and βâsheets of T4, human, and hen lysozymes and HI ribonuclease. The determined energies of vdW interactions and Hâbonds were smaller than in molecular mechanics and followed the âlike dissolves likeâ rule, as expected in condensed media but not in vacuum. The depths of modified LennardâJones potentials were â0.34, â0.12, and â0.06 kcal/mole for similar atom types (polarâpolar, aromaticâaromatic, and aliphaticâaliphatic interactions, respectively) and â0.10, â0.08, â0.06, â0.02, and nearly 0 kcal/mole for different types (sulfurâpolar, sulfurâaromatic, sulfurâaliphatic, aliphaticâaromatic, and carbonâpolar, respectively), whereas the depths of Hâbond potentials were â1.5 to â1.8 kcal/mole. The obtained solvation parameters, that is, transfer energies from water to the protein interior, were 19, 7, â1, â21, and â66 cal/moleĂ
2 for aliphatic carbon, aromatic carbon, sulfur, nitrogen, and oxygen, respectively, which is close to the cyclohexane scale for aliphatic and aromatic groups but intermediate between octanol and cyclohexane for others. An analysis of additional replacements at the waterâprotein interface indicates that vdW interactions between protein atoms are reduced when they occur across water.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106915/1/111984_ftp.pd
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