Flying insects typically possess two pairs of wings. In beetles, the front pair has evolved into short, hardened structures, the elytra, which protect the second pair of wings and the abdomen. This allows beetles to exploit habitats that would otherwise cause damage to the wings and body. Many beetles fly with the elytra extended, suggesting that they influence aerodynamic performance, but little is known about their role in flight. Using quantitative measurements of the beetle's wake, we show that the presence of the elytra increases vertical force production by approximately 40 per cent, indicating that they contribute to weight support. The wing-elytra combination creates a complex wake compared with previously studied animal wakes. At mid-downstroke, multiple vortices are visible behind each wing. These include a wingtip and an elytron vortex with the same sense of rotation, a body vortex and an additional vortex of the opposite sense of rotation. This latter vortex reflects a negative interaction between the wing and the elytron, resulting in a single wing span efficiency of approximately 0.77 at mid downstroke. This is lower than that found in birds and bats, suggesting that the extra weight support of the elytra comes at the price of reduced efficiency.
beetles; flight; aerodynamics
Over the last decade, solid-binding peptides have been increasingly used as molecular building blocks coupling bio- and nanotechnology. Despite considerable research being invested in this field, the effects of many surface-related parameters that define the binding of peptide to solids are still unknown. In the quest to control biological molecules at solid interfaces and, thereby, tailoring the binding characteristics of the peptides, the use of surface charge of the solid surface may probably play an important role, which then can be used as a potential tuning parameter of peptide adsorption. Here, we report quantitative investigation on the viscoelastic properties and binding kinetics of an engineered gold-binding peptide, 3RGBP1, adsorbed onto the gold surface at different surface charge densities. The experiments were performed in aqueous solutions using an electrochemical dissipative quartz crystal microbalance system. Hydrodynamic mass, hydration state and surface coverage of the adsorbed peptide films were determined as a function of surface charge density of the gold metal substrate. Under each charged condition, binding of 3rGBP1 displayed quantitative differences in terms of adsorbed peptide amount, surface coverage ratio and hydration state. Based on the intrinsically disordered structure of the peptide, we propose a possible mechanism for binding of the peptide that can be used for tuning surface adsorption in further studies. Controlled alteration of peptide binding on solid surfaces, as shown here, may provide novel methods for surface functionalization used for bioenabled processing and fabrication of future micro- and nanodevices.
solid-binding peptides; gold; metal surface charge; molecular recognition; adsorption
Catastrophic regime shifts in complex natural systems may be averted through advanced detection. Recent work has provided a proof-of-principle that many systems approaching a catastrophic transition may be identified through the lens of early warning indicators such as rising variance or increased return times. Despite widespread appreciation of the difficulties and uncertainty involved in such forecasts, proposed methods hardly ever characterize their expected error rates. Without the benefits of replicates, controls or hindsight, applications of these approaches must quantify how reliable different indicators are in avoiding false alarms, and how sensitive they are to missing subtle warning signs. We propose a model-based approach to quantify this trade-off between reliability and sensitivity and allow comparisons between different indicators. We show these error rates can be quite severe for common indicators even under favourable assumptions, and also illustrate how a model-based indicator can improve this performance. We demonstrate how the performance of an early warning indicator varies in different datasets, and suggest that uncertainty quantification become a more central part of early warning predictions.
early warning signals; tipping point; alternative stable states; likelihood methods
Intensive care units (ICUs) play an important role in the epidemiology of methicillin-resistant Staphyloccocus aureus (MRSA). Although successful interventions are multi-modal, the relative efficacy of single measures remains unknown. We developed a discrete time, individual-based, stochastic mathematical model calibrated on cross-transmission observed through prospective surveillance to explore the transmission dynamics of MRSA in a medical ICU. Most input parameters were derived from locally acquired data. After fitting the model to the 46 observed cross-transmission events and performing sensitivity analysis, several screening and isolation policies were evaluated by simulating the number of cross-transmissions and isolation-days. The number of all cross-transmission events increased from 54 to 72 if only patients with a past history of MRSA colonization are screened and isolated at admission, to 75 if isolation is put in place only after the results of the admission screening become available, to 82 in the absence of admission screening and with a similar reactive isolation policy, and to 95 when no isolation policy is in place. The method used (culture or polymerase chain reaction) for admission screening had no impact on the number of cross-transmissions. Systematic regular screening during ICU stay provides no added-value, but aggressive admission screening and isolation effectively reduce the number of cross-transmissions. Critically, colonized healthcare workers may play an important role in MRSA transmission and their screening should be reinforced.
methicillin-resistant Staphyloccocus aureus; epidemiology; mathematical modelling
The specific recognition between monoclonal antibody (anti-human prostate-specific antigen, anti-hPSA) and its antigen (human prostate-specific antigen, hPSA) has promising applications in prostate cancer diagnostics and other biosensor applications. However, because of steric constraints associated with interfacial packing and molecular orientations, the binding efficiency is often very low. In this study, spectroscopic ellipsometry and neutron reflection have been used to investigate how solution pH, salt concentration and surface chemistry affect antibody adsorption and subsequent antigen binding. The adsorbed amount of antibody was found to vary with pH and the maximum adsorption occurred between pH 5 and 6, close to the isoelectric point of the antibody. By contrast, the highest antigen binding efficiency occurred close to the neutral pH. Increasing the ionic strength reduced antibody adsorbed amount at the silica–water interface but had little effect on antigen binding. Further studies of antibody adsorption on hydrophobic C8 (octyltrimethoxysilane) surface and chemical attachment of antibody on (3-mercaptopropyl)trimethoxysilane/4-maleimidobutyric acid N-hydroxysuccinimide ester-modified surface have also been undertaken. It was found that on all surfaces studied, the antibody predominantly adopted the ‘flat on’ orientation, and antigen-binding capabilities were comparable. The results indicate that antibody immobilization via appropriate physical adsorption can replace elaborate interfacial molecular engineering involving complex covalent attachments.
biointerface; interfacial binding; antibody binding; antigen recognition; neutron reflection; antibody conformation
We describe a novel tracking system for reconstructing three-dimensional tracks of individual mosquitoes in wild swarms and present the results of validating the system by filming swarms and mating events of the malaria mosquito Anopheles gambiae in Mali. The tracking system is designed to address noisy, low frame-rate (25 frames per second) video streams from a stereo camera system. Because flying A. gambiae move at 1–4 m s−1, they appear as faded streaks in the images or sometimes do not appear at all. We provide an adaptive algorithm to search for missing streaks and a likelihood function that uses streak endpoints to extract velocity information. A modified multi-hypothesis tracker probabilistically addresses occlusions and a particle filter estimates the trajectories. The output of the tracking algorithm is a set of track segments with an average length of 0.6–1 s. The segments are verified and combined under human supervision to create individual tracks up to the duration of the video (90 s). We evaluate tracking performance using an established metric for multi-target tracking and validate the accuracy using independent stereo measurements of a single swarm. Three-dimensional reconstructions of A. gambiae swarming and mating events are presented.
target tracking; Anopheles gambiae; mosquito swarms; mating mosquitoes
Unlike mammalian, disc-shaped intervertebral joints (IVJs), the IVJs in fishes are biconid structures, filled with fluid and thought to act as hydrostatic hinge joints during swimming. However, it remains unclear which IVJ structures are dominant in mechanical resistance to forces in fishes, and whether variation in these tissues might impact the function of the vertebral column along its length. Here, we measured the dynamic mechanical behaviour of IVJs from striped bass, Morone saxatilis. During lateral bending, angular stiffness was significantly lower in the caudal and cervical regions, relative to the abdominal region. The neutral zone, defined as the range of motion (ROM) at bending moments less than 0.001 Nm, was longer in the caudal relative to the abdominal IVJs. Hysteresis was 30–40% in all regions, suggesting that IVJs may play a role in energy dissipation during swimming. Cutting the vertical septum had no statistically significant effect, but cutting the encapsulating tissues caused a sharp decline in angular stiffness and a substantial increase in ROM and hysteresis. We conclude that stiffness decreases and ROM increases from cranial to caudal in striped bass, and that the encapsulating tissues play a prominent role in mechanical variation along the length of the vertebral column.
biomechanics; vertebral column; intervertebral joints; striped bass; Morone saxatilis
Cellular communication depends on membrane fusion mechanisms. SNARE proteins play a fundamental role in all intracellular fusion reactions associated with the life cycle of secretory vesicles, such as vesicle–vesicle and vesicle plasma membrane fusion at the porosome base in the cell plasma membrane. We present growth and elimination (G&E), a birth and death model for the investigation of granule growth, its evoked and spontaneous secretion and their information content. Using a statistical mechanics approach in which SNARE components are viewed as interacting particles, the G&E model provides a simple ‘nano-machine’ of SNARE self-aggregation behind granule growth and secretion. Results from experimental work, mathematical calculations and statistical modelling suggest that for vesicle growth a minimal aggregation of three SNAREs is required, while for the evoked secretion one SNARE is enough. Furthermore, the required number of SNARE aggregates (which varies between cell types and is nearly proportional to the square root of the mean granule diameter) affects and is statistically identifiable from the size distributions of spontaneous and evoked secreted granules. The new statistical mechanics approach to granule fusion is bound to have a significant changing effect on the investigation of the pathophysiology of secretory mechanisms and methodologies for the investigation of secretion.
cellular communication; homotypic fusion; porosome; SNARE; unit granule
Here, we show that the local incorporation of osmotically active hyaluronan into previously compressed collagen constructs results in further rapid dehydration/compression of collagen layers, channel formation and generation of new interfaces; these novel structures, at the nano–micro (i.e. meso-scale) were formed within native collagen gels, in a highly predictable spatial manner and offer important new methods of fabricating scaffolds (e.g. tubes and open-spirals) with potential for use in tissue regeneration such as in peripheral nerves and small vessels. This paper tests the possibility that the local fluid content of a dense collagen network can be controlled by incorporation of an osmotically active (native) macromolecule—hyluronan. This is an exemplar physiological, osmotic swelling agent. Hyaluronan is commonly secreted by cells deep in connective tissues, so is a good candidate for this role in a cell-driven system balancing mechanical compaction of bulk tissue collagen. These constructs may have potential as functional in vitro models representing developmental and pathological processes.
collagen; biomaterials; tissue regeneration; hyaluronan
Poly(lactic-co-glycolic acid) (PLGA) microspheres containing celecoxib were prepared via electrospraying, and the influence of three processing parameters namely flow rate, solute concentration and drug loading, on the physico-chemical properties of the particles and the drug-release profile was studied. Microspheres with diameters between 2 and 8 μm were produced and a near-monodisperse size distribution was achieved (polydispersivity indices of 6–12%). Further, the inner structure of the particles showed that the internal porosity of the particles increased with increasing solvent concentration. X-ray powder diffraction (XRPD) analysis indicated that the drug was amorphous and remained stable after eight months of storage. Drug release was studied in USP 2 (United States Pharmacopeia Dissolution Apparatus 2) dissolution chambers, and differences in release profiles were observed depending on the parametric values. Changes in release rate were found to be directly related to the influence of the studied parameters on particle size and porosity. The results indicate that electrospraying is an attractive technique for producing drug-loaded microspheres that can be tailored towards an intended drug-delivery application. Compared with the more conventional spray-drying process, it provides better control of particle characteristics and less aggregation during particle formation. In particular, this study demonstrated its suitability for preparing capsules in which the drug is molecularly dispersed and released in a sustained manner to facilitate improved bioavailability.
controlled release; microspheres; electrospraying; low solubility; celecoxib; porosity
Natural selection favours phenotypes that match prevailing ecological conditions. A rapid process of adaptation is therefore required in changing environments. Maternal effects can facilitate such responses, but it is currently poorly understood under which circumstances maternal effects may accelerate or slow down the rate of phenotypic evolution. Here, we use a quantitative genetic model, including phenotypic plasticity and maternal effects, to suggest that the relationship between fitness and phenotypic variance plays an important role. Intuitive expectations that positive maternal effects are beneficial are supported following an extreme environmental shift, but, if too strong, that shift can also generate oscillatory dynamics that overshoot the optimal phenotype. In a stable environment, negative maternal effects that slow phenotypic evolution actually minimize variance around the optimum phenotype and thus maximize population mean fitness.
maternal inheritance; maternal effects; quantitative genetics; evolutionary dynamics
The hunting spider Cupiennius salei uses airflow generated by flying insects for the guidance of its prey-capture jump. We investigated the velocity field of the airflow generated by a freely flying blowfly close to the flow sensors on the spider's legs. It shows three characteristic phases (I–III). (I) When approaching, the blowfly induces an airflow signal near the spider with only little fluctuation (0.013 ± 0.006 m s−1) and a strength that increases nearly exponentially with time (maximum: 0.164 ± 0.051 m s−1 s.d.). The spider detects this flow while the fly is still 38.4 ± 5.6 mm away. The fluctuation of the airflow above the sensors increases linearly up to 0.037 m s−1 with the fly's altitude. Differences in the time of arrival and intensity of the fly signal at different legs probably inform the spider about the direction to the prey. (II) Phase II abruptly follows phase I with a much higher degree of fluctuation (fluctuation amplitudes: 0.114 ± 0.050 m s−1). It starts when the fly is directly above the sensor and corresponds to the time-dependent flow in the wake below and behind the fly. Its onset indicates to the spider that its prey is now within reach and triggers its jump. The spider derives information on the fly's position from the airflow characteristics, enabling it to properly time its jump. The horizontal velocity of the approaching fly is reflected by the time of arrival differences (ranging from 0.038 to 0.108 s) of the flow at different legs and the exponential velocity growth rate (16–79 s−1) during phase I. (III) The air flow velocity decays again after the fly has passed the spider.
spider; blowfly; flow field; particle image velocimetry; orientation; prey capture
Non-iridescent structural colours of feathers are a diverse and an important part of the phenotype of many birds. These colours are generally produced by three-dimensional, amorphous (or quasi-ordered) spongy β-keratin and air nanostructures found in the medullary cells of feather barbs. Two main classes of three-dimensional barb nanostructures are known, characterized by a tortuous network of air channels or a close packing of spheroidal air cavities. Using synchrotron small angle X-ray scattering (SAXS) and optical spectrophotometry, we characterized the nanostructure and optical function of 297 distinctly coloured feathers from 230 species belonging to 163 genera in 51 avian families. The SAXS data provided quantitative diagnoses of the channel- and sphere-type nanostructures, and confirmed the presence of a predominant, isotropic length scale of variation in refractive index that produces strong reinforcement of a narrow band of scattered wavelengths. The SAXS structural data identified a new class of rudimentary or weakly nanostructured feathers responsible for slate-grey, and blue-grey structural colours. SAXS structural data provided good predictions of the single-scattering peak of the optical reflectance of the feathers. The SAXS structural measurements of channel- and sphere-type nanostructures are also similar to experimental scattering data from synthetic soft matter systems that self-assemble by phase separation. These results further support the hypothesis that colour-producing protein and air nanostructures in feather barbs are probably self-assembled by arrested phase separation of polymerizing β-keratin from the cytoplasm of medullary cells. Such avian amorphous photonic nanostructures with isotropic optical properties may provide biomimetic inspiration for photonic technology.
biophotonics; organismal structural colours; amorphous nanostructures; non-iridescence; single scattering; self-assembly
Despite successful fabrication of gecko-inspired fibrillar surfaces with strong adhesion forces, how to achieve an easy-removal property becomes a major concern that may restrict the wide applications of these bio-inspired surfaces. Research on how geckos detach rapidly has inspired the design of novel adhesive surfaces with strong and reversible adhesion capabilities, which relies on further fundamental understanding of the peeling mechanisms. Recent studies showed that the peel-zone plays an important role in the peeling off of adhesive tapes or fibrillar surfaces. In this study, a numerical method was developed to evaluate peel-zone deformation and the resulting mechanical behaviour due to the deformations of fibrillar surfaces detaching from a smooth rigid substrate. The effect of the geometrical parameters of pillars and the stiffness of backing layer on the peel-zone and peel strength, and the strong attachment and easy-removal properties have been analysed to establish a design map for bio-inspired fibrillar surfaces, which shows that the optimized strong attachment and easy-removal properties can vary by over three orders of magnitude. The adhesion and peeling design map established provides new insights into the design and development of novel gecko-inspired fibrillar surfaces.
gecko-inspired surface; peel zone; easy removal; adhesion and peeling design map
An overwhelming majority of humans are right-handed. Numerous explanations for individual handedness have been proposed, but this population-level handedness remains puzzling. Here, we present a novel mathematical model and use it to test the idea that population-level hand preference represents a balance between selective costs and benefits arising from cooperation and competition in human evolutionary history. We use the selection of elite athletes as a test-bed for our evolutionary model and find evidence for the validity of this idea. Our model gives the first quantitative explanation for the distribution of handedness both across and within many professional sports. It also predicts strong lateralization of hand use in social species with limited combative interaction, and elucidates the absence of consistent population-level ‘pawedness’ in some animal species.
evolution; handedness; laterality; mathematical model
Hydrophobins are small proteins secreted by fungi, which self-assemble into amphipathic membranes at air–liquid or liquid–solid interfaces. The physical and chemical properties of some hydrophobins, both in solution and as a biofilm, are affected by poly or oligosaccharides. We have studied the interaction between glucose and the hydrophobin Vmh2 from Pleurotus ostreatus by spectroscopic ellipsometry (SE), atomic force microscopy (AFM) and water contact angle (WCA). We have found that Vmh2–glucose complexes forms a chemically stable biofilm, obtained by drop deposition on silicon, 1.6 nm thick and containing 35 per cent of glucose, quantified by SE. AFM highlighted the presence of nanometric rodlet-like aggregates (average height, width and length being equal to 3.6, 23.8 and 40 nm, respectively) on the biofilm surface, slightly different from those obtained in the absence of glucose (4.11, 23.9 and 64 nm). The wettability of a silicon surface, covered by the organic layer of Vmh2–glucose, strongly changed: WCA decreased from 90° down to 17°.
surface modification; protein biofilm; spectroscopic ellipsometry; atomic force microscopy
To test the hypothesis that disturbed flow can impede the transport of nitric oxide (NO) in the artery and hence induce atherogenesis, we used a lumen–wall model of an idealized arterial stenosis with NO produced at the blood vessel–wall interface to study the transport of NO in the stenosis. Blood flows in the lumen and through the arterial wall were simulated by Navier–Stokes equations and Darcy's Law, respectively. Meanwhile, the transport of NO in the lumen and the transport of NO within the arterial wall were modelled by advection–diffusion reaction equations. Coupling of fluid dynamics at the endothelium was achieved by the Kedem–Katchalsky equations. The results showed that both the hydraulic conductivity of the endothelium and the non-Newtonian viscous behaviour of blood had little effect on the distribution of NO. However, the blood flow rate, stenosis severity, red blood cells (RBCs), RBC-free layer and NO production rate at the blood vessel–wall interface could significantly affect the transport of NO. The theoretical study revealed that the transport of NO was significantly hindered in the disturbed flow region distal to the stenosis. The reduced NO concentration in the disturbed flow region might play an important role in the localized genesis and development of atherosclerosis.
nitric oxide; atherogenesis; disturbed flow; mathematical model
Chitosan (CS), the deacetylated form of chitin, the second most abundant, natural polysaccharide, is attractive for applications in the biomedical field because of its biocompatibility and resorption rates, which are higher than chitin. Crosslinking improves chemical and mechanical stability of CS. Here, we report the successful utilization of a new set of crosslinkers for electrospun CS. Genipin, hexamethylene-1,6-diaminocarboxysulphonate (HDACS) and epichlorohydrin (ECH) have not been previously explored for crosslinking of electrospun CS. In this first part of a two-part publication, we report the morphology, determined by field emission scanning electron microscopy (FESEM), and chemical interactions, determined by Fourier transform infrared microscopy, respectively. FESEM revealed that CS could successfully be electrospun from trifluoroacetic acid with genipin, HDACS and ECH added to the solution. Diameters were 267 ± 199 nm, 644 ± 359 nm and 896 ± 435 nm for CS–genipin, CS–HDACS and CS–ECH, respectively. Short- (15 min) and long-term (72 h) dissolution tests (T600) were performed in acidic, neutral and basic pHs (3, 7 and 12). Post-spinning activation by heat and base to enhance crosslinking of CS–HDACS and CS–ECH decreased the fibre diameters and improved the stability. In the second part of this publication, we report the mechanical properties of the fibres.
electrospinning; chitosan; biopolymer; genipin; diisocyanate; epichlorohydrin
Bistability is a fundamental phenomenon in nature. In biology, a number of fine properties of bistability have been identified. However, these properties are only consequences of bistability at the physiological level, which do not explain why it had to emerge during evolution. Using optimal homeostasis as the first principle, I find that bistability emerges as an indispensable control mechanism. It is the only solution to a dilemma in glucose homeostasis: high insulin efficiency is required to confer rapidness in plasma glucose clearance, whereas an insulin sparing state is required to guarantee the brain's safety during fasting. The optimality consideration renders a clear correspondence between the molecular and physiological levels. This new perspective can illuminate studies on the twin epidemics of obesity and diabetes and the corresponding intervening strategies. For example, overnutrition and sedentary lifestyle may represent sudden environmental changes that cause the lose of optimality, which may contribute to the marked rise of obesity and diabetes in our generation. Because this bistability result is independent of the parameters of the mathematical model (for which the result is quite general), some other biological systems may also use bistability to control homeostasis.
bistability; homeostasis; optimal control; glucose–insulin feedback system; insulin signalling pathway; AKT
We study the temporal evolution of the structure of the world's largest subway networks in an exploratory manner. We show that, remarkably, all these networks converge to a shape that shares similar generic features despite their geographical and economic differences. This limiting shape is made of a core with branches radiating from it. For most of these networks, the average degree of a node (station) within the core has a value of order 2.5 and the proportion of k = 2 nodes in the core is larger than 60 per cent. The number of branches scales roughly as the square root of the number of stations, the current proportion of branches represents about half of the total number of stations, and the average diameter of branches is about twice the average radial extension of the core. Spatial measures such as the number of stations at a given distance to the barycentre display a first regime which grows as r2 followed by another regime with different exponents, and eventually saturates. These results—difficult to interpret in the framework of fractal geometry—confirm and yield a natural explanation in the geometric picture of this core and their branches: the first regime corresponds to a uniform core, while the second regime is controlled by the interstation spacing on branches. The apparent convergence towards a unique network shape in the temporal limit suggests the existence of dominant, universal mechanisms governing the evolution of these structures.
evolution of networks; urban transportation; spatial networks; core and branch geometry
During development, epithelial tissues undergo extensive morphogenesis based on coordinated changes of cell shape and position over time. Continuum mechanics describes tissue mechanical state and shape changes in terms of strain and stress. It accounts for individual cell properties using only a few spatially averaged material parameters. To determine the mechanical state and parameters in the Drosophila pupa dorsal thorax epithelium, we severed in vivo the adherens junctions around a disc-shaped domain comprising typically a hundred cells. This enabled a direct measurement of the strain along different orientations at once. The amplitude and the anisotropy of the strain increased during development. We also measured the stress-to-viscosity ratio and similarly found an increase in amplitude and anisotropy. The relaxation time was of the order of 10 s. We propose a space–time, continuous model of the relaxation. Good agreement with experimental data validates the description of the epithelial domain as a continuous, linear, visco-elastic material. We discuss the relevant time and length scales. Another material parameter, the ratio of external friction to internal viscosity, is estimated by fitting the initial velocity profile. Together, our results contribute to quantify forces and displacements, and their time evolution, during morphogenesis.
epithelial tissue; continuum mechanics; laser severing; Drosophila development; live imaging
In the current study, the mechanical and hypothermic damage induced by vibration and cold storage on human mesenchymal stem cells (hMSCs) stored at 2–8°C was quantified by measuring the total cell number and cell viability after exposure to vibration at 50 Hz (peak acceleration 140 m s−2 and peak displacement 1.4 mm), 25 Hz (peak acceleration 140 m s−2, peak displacement 5.7 mm), 10 Hz (peak acceleration 20 m s−2, peak displacement 5.1 mm) and cold storage for several durations. To quantify the viability of the cells, in addition to the trypan blue exclusion method, the combination of annexin V-FITC and propidium iodide was applied to understand the mode of cell death. Cell granularity and a panel of cell surface markers for stemness, including CD29, CD44, CD105 and CD166, were also evaluated for each condition. It was found that hMSCs were sensitive to vibration at 25 Hz, with moderate effects at 50 Hz and no effects at 10 Hz. Vibration at 25 Hz also increased CD29 and CD44 expression. The study further showed that cold storage alone caused a decrease in cell viability, especially after 48 h, and also increased CD29 and CD44 and attenuated CD105 expressions. Cell death would most likely be the consequence of membrane rupture, owing to necrosis induced by cold storage. The sensitivity of cells to different vibrations within the mechanical system is due to a combined effect of displacement and acceleration, and hMSCs with a longer cold storage duration were more susceptible to vibration damage, indicating a coupling between the effects of vibration and cold storage.
stem cells; mechanical stress; vibration; regenerative medicine; hypothermia; viability
Phenotypic variation facilitates adaptations to novel environments. Silk is an example of a highly variable biomaterial. The two-spidroin (MaSp) model suggests that spider major ampullate (MA) silk is composed of two proteins—MaSp1 predominately contains alanine and glycine and forms strength enhancing β-sheet crystals, while MaSp2 contains proline and forms elastic spirals. Nonetheless, mechanical properties can vary in spider silks without congruent amino acid compositional changes. We predicted that post-secretion processing causes variation in the mechanical performance of wild MA silk independent of protein composition or spinning speed across 10 species of spider. We used supercontraction to remove post-secretion effects and compared the mechanics of silk in this ‘ground state’ with wild native silks. Native silk mechanics varied less among species compared with ‘ground state’ silks. Variability in the mechanics of ‘ground state’ silks was associated with proline composition. However, variability in native silks did not. We attribute interspecific similarities in the mechanical properties of native silks, regardless of amino acid compositions, to glandular processes altering molecular alignment of the proteins prior to extrusion. Such post-secretion processing may enable MA silk to maintain functionality across environments, facilitating its function as a component of an insect-catching web.
biomaterial plasticity; MaSp expression model; mechanical properties; orb web; spider silk; supercontraction
Medical and pharmacological communities have long searched for antimicrobial drugs that increase their effect when used in combination, an interaction known as synergism. These drug combinations, however, impose selective pressures in favour of multi-drug resistance and as a result, the benefit of synergy may be lost after only a few bacterial generations. Furthermore, there is experimental evidence that antibiotic treatment can disrupt colonization resistance by shifting the balance between enteropathogenic and commensal bacteria in favour of the pathogens, with the potential to increase the risk of infections. So, we ask, what is the best way of using synergistic drugs? We pose an evolutionary model of commensal and pathogenic bacteria competing in a continuous culture device for a single limiting carbon source under the effect of two bacteriostatic and synergistic antibiotics. This model allows us to evaluate the efficacy of different drug deployment strategies and, using ideas from optimal control theory, to understand whether there are circumstances in which other types of therapy might be favoured over those based on fixed-dose multi-drug combinations. Our main result can be stated thus: the optimal deployment of synergistic antibiotics to remove a pathogen in the presence of commensal bacteria in our model system occurs not in combination, but by deploying them sequentially.
antimicrobial resistance; drug interactions; control theory
The osteocyte is believed to act as the main sensor of mechanical stimulus in bone, controlling signalling for bone growth and resorption in response to changes in the mechanical demands placed on our bones throughout life. However, the precise mechanical stimuli that bone cells experience in vivo are not yet fully understood. The objective of this study is to use computational methods to predict the loading conditions experienced by osteocytes during normal physiological activities. Confocal imaging of the lacunar–canalicular network was used to develop three-dimensional finite element models of osteocytes, including their cell body, and the surrounding pericellular matrix (PCM) and extracellular matrix (ECM). We investigated the role of the PCM and ECM projections for amplifying mechanical stimulation to the cells. At loading levels, representing vigorous physiological activity (3000 µɛ), our results provide direct evidence that (i) confocal image-derived models predict 350–400% greater strain amplification experienced by osteocytes compared with an idealized cell, (ii) the PCM increases the cell volume stimulated more than 3500 µɛ by 4–10% and (iii) ECM projections amplify strain to the cell by approximately 50–420%. These are the first confocal image-derived computational models to predict osteocyte strain in vivo and provide an insight into the mechanobiology of the osteocyte.
bone; osteocyte; mechanobiology; lacuna; pericellular matrix; tissue strain