Comprehensive characterization of molecular interactions based on nanomechanics

Molecular interaction is a key concept in our understanding of the biological mechanisms of life. Two physical properties change when one molecular partner binds to another. Firstly, the masses combine and secondly, the structure of at least one binding partner is altered, mechanically transducing the binding into subsequent biological reactions. Here we present a nanomechanical micro-array technique for bio-medical research, which not only monitors the binding of effector molecules to their target but also the subsequent effect on a biological system in vitro. This label-free and real-time method directly and simultaneously tracks mass and nanomechanical changes at the sensor interface using micro-cantilever technology. To prove the concept we measured lipid vesicle (approximately 748*10(6) Da) adsorption on the sensor interface followed by subsequent binding of the bee venom peptide melittin (2840 Da) to the vesicles. The results show the high dynamic range of the instrument and that measuring the mass and structural changes simultaneously allow a comprehensive discussion of molecular interactions

Nanomechanical detection of antibiotic-mucopeptide binding in a model for superbug drug resistance

The alarming growth of the antibiotic-resistant superbugs methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) is driving the development of new technologies to investigate antibiotics and their modes of action. We report the label-free detection of vancomycin binding to bacterial cell wall precursor analogues (mucopeptides) on cantilever arrays, with 10 nM sensitivity and at clinically relevant concentrations in blood serum. Differential measurements quantified binding constants for vancomycin-sensitive and vancomycin-resistant mucopeptide analogues. Moreover, by systematically modifying the mucopeptide density we gain new insights into the origin of surface stress. We propose that stress is a product of a local chemical binding factor and a geometrical factor describing the mechanical connectivity of regions affected by local binding in terms of a percolation process. Our findings place BioMEMS devices in a new class of percolative systems. The percolation concept will underpin the design of devices and coatings to significantly lower the drug detection limit and may also impact on our understanding of antibiotic drug action in bacteria.Comment: Comments: This paper consists of the main article (6 pages, 5 figures) plus Supplemental Material (6 pages, 3 figures). More details are available at http://www.london-nano.co

I Tensed the Laws and the Laws Won: Non-Eternalist Humeanism

ABSTRACT In this paper, I propose a variant of a Humean account of laws called "Open Future Humeanism" (OFH), which holds that since the laws supervene partly on future events, there are at any instant infinitely many possible future courses of events. I argue that if one wants to take the openness of the future that OFH proposes ontologically serious, then OFH is best represented within a growing block view of time. I further discuss some of OFH's problems which stem from the fact that in this view, there are no laws as long as time progresses. These problems can be solved by adding a temporal operator to the laws, so that at any instant, we get a set of tensed laws which held up to and including that instant

Digital processing of multi-mode nano-mechanical cantilever data

Nanomechanical sensors based on cantilever technology allow the measurement of various physical properties. Here we present a software for the comprehensive analysis of such data. An example for the combined measurement of mass and surface stress is presented

A new family of intrinsically disordered proteins: structural characterization of the major phasin PhaF from Pseudomonas putida KT2440

Contains fulltext : 118281.pdf (publisher's version ) (Open Access)Phasins are intracellular polyhydroxyalkanoat4e (PHA)-associated proteins involved in the stabilization of these bacterial carbon storage granules. Despite its importance in PHA metabolism and regulation, only few reports have focused so far on the structure of these proteins. In this work we have investigated the structure and stability of the PhaF phasin from Pseudomonas putida KT2440, a protein that is involved in PHA granule stabilization and distribution to daughter cells upon cell division. A structural, three-dimensional model of the protein was built from homology modeling procedures and consensus secondary structure predictions. The model predicts that PhaF is an elongated protein, with a long, amphipathic N-terminal helix with PHA binding capacity, followed by a short leucine zipper involved in protein oligomerization and a superhelical C-terminal domain wrapped around the chromosomal DNA. Hydrodynamic, spectroscopical and thermodynamic experiments validated the model and confirmed both that free PhaF is a tetramer in solution and that most part of the protein is intrinsically disordered in the absence of its ligands. The results lay a molecular basis for the explanation of the biological role of PhaF and, along with an exhaustive analysis of phasin sequence databases, suggest that intrinsic disorder and oligomerization through coiled-coils may be a widespread mechanism among these proteins

A comparative perspective on teacher attitude-constructs that impact on inclusive education in South Africa and Sweden

This article is based on joint research, between academics from South Africa and Sweden, comparing the influence of South African and Swedish teachers' attitudes towards the practical application of inclusive education (IE) in the classroom. The aim of the study was to identify and investigate problem areas pertaining to teachers' attitudes to IE. Attitudes often relate to interaction with others. This study departs from Festiger's theory of cognitive dissonance, which deals with the influence of people's attitudes and attitude change. In this research teachers from South Africa and Sweden completed the same questionnaire on perceptions pertaining to IE in their school system. A number of attitude-constructs were derived from the data via exploratory factor analysis methodology. Attitude-constructs included policy issues and specialised support; practical implementation of IE; teacher support structures; teachers' receptiveness of IE implementation; feasibility of proposed IE practices; and role of special schools in an IE environment. Negative responses to some of the attitude constructs identified problem areas in Swedish and South African inclusive systems. The comparative nature of the work enabled the researchers to suggest remedial action within each country's socio-economic setting, and in this way affect change in teacher attitudes. © 2011 EASA

Towards a modular, versatile and portable sensor system for measurements in gaseous environments based on microcantilevers

AbstractMicrofabricated silicon cantilever sensor arrays represent a powerful platform for sensing applications in physics, chemistry, material science, biology and medicine. The sensor response is mechanical bending due to absorption of molecules. In gaseous environment, polymer-coated microcantilevers are used as electronic nose for characterization of vapors, resulting in cantilever bending due to polymer swelling upon exposure. Medical applications involve fast characterization of exhaled patient's breath samples for detection of diseases, based on the presence of certain chemicals in breath. We present a portable, compact, modular microcantilever setup, which uses a micropump for aspiration and a bluetooth interface for remote data acquisition