Antibiotic Potential and Biophysical Characterization of Amphipathic β-Stranded [XZ]n Peptides With Alternating Cationic and Hydrophobic Residues

Cationic membrane-active peptides are considered to be promising candidates for antibiotic treatment. Many natural and artificial sequences show an antimicrobial activity when they are able to take on an amphipathic fold upon membrane binding, which in turn perturbs the integrity of the lipid bilayer. Most known structures are α-helices and β-hairpins, but also cyclic knots and other irregular conformations are known. Linear β-stranded antimicrobial peptides are not so common in nature, but numerous model sequences have been designed. Interestingly, many of them tend to be highly membranolytic, but also have a significant tendency to self-assemble into β-sheets by hydrogen-bonding. In this minireview we examine the literature on such amphipathic peptides consisting of simple repetitive sequences of alternating cationic and hydrophobic residues, and discuss their advantages and disadvantages. Their interactions with lipids have been characterized with a number of biophysical techniques—especially circular dichroism, fluorescence, and infrared—in order to determine their secondary structure, membrane binding, aggregation tendency, and ability to permeabilize vesicles. Their activities against bacteria, biofilms, erythrocytes, and human cells have also been studied using biological assays. In line with the main scope of this Special Issue, we attempt to correlate the biophysical results with the biological data, and in particular we discuss which properties (length, charge, aggregation tendency, etc.) of these simple model peptides are most relevant for their biological function. The overview presented here offers ideas for future experiments, and also suggests a few design rules for promising β-stranded peptides to develop efficient antimicrobial agents

Gait Based Vertical Ground Reaction Force Analysis for Parkinson's Disease Diagnosis Using Self Organizing Map

ABSTRACT The aim of this work is to use Self Organizing Map (SOM) for clustering of locomotion kinetic characteristics in normal and Parkinson's disease. The classification and analysis of the kinematic characteristics of human locomotion has been greatly increased by the use of artificial neural networks in recent years. The proposed methodology aims at overcoming the constraints of traditional analysis methods and to find new clinical ways for observing the large amount of information obtained in a gait lab. Self organizing maps (SOM) also called Kohonen maps are a special kind of neural networks that can be used for clustering tasks. The results are shown in the terms of sensitivity, specificity, accuracy, error rate from the two groups of features which are the Mean Coefficient of Variation and Mean Sum of Variation and Mean Max and Mean Standard deviation of the Ground Reaction Force. Results showing the potential of this technique for distinguishing between population of individuals with normal gait and with gait disorders of different causes of disease

Synergistic Insertion of Antimicrobial Magainin-Family Peptides in Membranes Depends on the Lipid Spontaneous Curvature

AbstractPGLa and magainin 2 (MAG2) are amphiphilic antimicrobial peptides from frog skin with known synergistic activity. The orientation of the two helices in membranes was studied using solid-state 15N-NMR, for each peptide alone and for a 1:1 mixture of the peptides, in a range of different lipid systems. Two types of orientational behavior emerged. 1), In lipids with negative spontaneous curvature, both peptides remain flat on the membrane surface, when assessed both alone and in a 1:1 mixture. 2), In lipids with positive spontaneous curvature, PGLa alone assumes a tilted orientation but inserts into the bilayer in a transmembrane alignment in the presence of MAG2, whereas MAG2 stays on the surface or gets only slightly tilted, when observed both alone and in the presence of PGLa. The behavior of PGLa alone is identical to that of another antimicrobial peptide, MSI-103, in the same lipid systems, indicating that the curvature-dependent helix orientation is a general feature of membrane-bound peptides and also influences their synergistic intermolecular interactions

DNA-Directed Assembly of a Cell-Responsive Biohybrid Interface for Cargo Release

The development of a DNA-based cell-responsive biohybrid interface that can be used for spatially confined release of molecular cargo is reported. To this end, tailored DNA–protein conjugates are designed as gatekeepers that can be specifically cleaved by matrix metalloproteases (MMPs), which are secreted by many cancer cells. These gatekeepers can be installed by DNA hybridization on the surface of mesoporous silica nanoparticles (MSNs). The MSNs display another orthogonal DNA oligonucleotide that can be exploited for site-selective immobilization on solid glass surfaces to yield micropatterned substrates for cell adhesion. Using the human fibrosarcoma cell line HT1080 that secretes MMPs, it is demonstrated that the biohybrid surface is specifically modified by the cells to release both MSN-bound gatekeeper proteins and the encapsulated cargo peptide KLA. In view of the enormously high modularity of the system presented here, this approach promising for applications in drug delivery, tissue engineering, or other areas of nanobiotechnology is considered

Orthogonal protein decoration of DNA nanostructures based on SpyCatcher–SpyTag interaction

We present an efficient and readily applicable strategy for the covalent ligation of proteins to DNA origami by using the SpyCatcher–SpyTag (SC–ST) connector system. This approach showed orthogonality with other covalent connectors and has been used exemplarily for the immobilization and study of stereoselective ketoreductases to gain insight into the spatial arrangement of enzymes on DNA nanostructures

An open multi-physics framework for modelling wildland-urban interface fire evacuations

Fire evacuations at wildland-urban interfaces (WUI) pose a serious challenge to the emergency services, and are a global issue affecting thousands of communities around the world. This paper presents a multi-physics framework for the simulation of evacuation in WUI wildfire incidents, including three main modelling layers: wildfire, pedestrians, and traffic. Currently, these layers have been mostly modelled in isolation and there is no comprehensive model which accounts for their integration. The key features needed for system integration are identified, namely: consistent level of refinement of each layer (i.e. spatial and temporal scales) and their application (e.g. evacuation planning or emergency response), and complete data exchange. Timelines of WUI fire events are analysed using an approach similar to building fire engineering (available vs. required safe egress times for WUI fires, i.e. WASET/WRSET). The proposed framework allows for a paradigm shift from current wildfire risk assessment and mapping tools towards dynamic fire vulnerability mapping. This is the assessment of spatial and temporal vulnerabilities based on the wildfire threat evolution along with variables related to the infrastructure, population and network characteristics. This framework allows for the integration of the three main modelling layers affecting WUI fire evacuation and aims at improving the safety of WUI communities by minimising the consequences of wildfire evacuations