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

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

Targeting and tracing antigens in live cells with fluorescent nanobodies

We fused the epitope-recognizing fragment of heavy-chain antibodies from Camelidae sp. with fluorescent proteins to generate fluorescent, antigen-binding nanobodies (chromobodies) that can be expressed in living cells. We demonstrate that chromobodies can recognize and trace antigens in different subcellular compartments throughout S phase and mitosis. Chromobodies should enable new functional studies, as potentially any antigenic structure can be targeted and traced in living cells in this fashion

Psychological resilience of entrepreneurs: A review and agenda for future research

Given that entrepreneurs face substantial adversity in initiating and developing new ventures, a burgeoning stream of research has sought to understand the concept of entrepreneurs’ psychological resilience. To structure and synthesize what we know about entrepreneurs’ psychological resilience, we systematically review the empirical literature to provide insights on how it has been conceptualized and operationalized, along with its key antecedents and outcomes. Based on our review, we advance a promising agenda for future research, grounded in connecting the psychological resilience of entrepreneurs to other research areas connected to the new venture development process. Overall, we point to the urgent need for theoretical precision to enhance the utility of empirical contributions, suggest promising research designs, expand on the important role of adversity, discuss potential boundary conditions, elaborate on the link between entrepreneurs’ psychological resilience and organizational resilience, and address the potential dark side of resilience