15 research outputs found
Integrating materials and life sciences toward the engineering of biomimetic materials
Research in the field of biological and biomimetic materials constitutes a case study of how traditional research boundaries are becoming increasingly obsolete. Positioned at the intersection of life and physical sciences, it is becoming more and more evident that future development in this area will require extensive interaction between materials and life scientists. To highlight this cross-talking, we provide a brief overview of the field, intended to illustrate how these disciplines can be integrated. We start with a short historical perspective, emphasizing the role of biologists in initiating early studies in the field. In the second part of the paper, a summary of important biochemical concepts and techniques relevant to biological materials is presented, with the goal of guiding nonspecialists towards the relevant techniques and knowledge required to investigate potential model systems. In the third part, we describe two case studies that emphasize the critical role of biosynthesis in understanding structureâfunctionâproperty relationships in biological materials. We conclude with some remarks related to our own perception of how integration of materials and life sciences will lead to future developments in the field
Infiltration of chitin by protein coacervates defines the squid beak mechanical gradient.
The beak of the jumbo squid Dosidicus gigas is a fascinating example of how seamlessly nature builds with mechanically mismatched materials. A 200-fold stiffness gradient begins in the hydrated chitin of the soft beak base and gradually increases to maximum stiffness in the dehydrated distal rostrum. Here, we combined RNA-Seq and proteomics to show that the beak contains two protein families. One family consists of chitin-binding proteins (DgCBPs) that physically join chitin chains, whereas the other family comprises highly modular histidine-rich proteins (DgHBPs). We propose that DgHBPs play multiple key roles during beak bioprocessing, first by forming concentrated coacervate solutions that diffuse into the DgCBP-chitin scaffold, and second by inducing crosslinking via an abundant GHG sequence motif. These processes generate spatially controlled desolvation, resulting in the impressive biomechanical gradient. Our findings provide novel molecular-scale strategies for designing functional gradient materials
Biomimetic production of silk-like recombinant squid sucker ring teeth proteins
The sucker ring teeth (SRT) of Humboldt squid exhibit mechanical properties that rival those of robust engineered synthetic polymers. Remarkably, these properties are achieved without a mineral phase or covalent cross-links. Instead, SRT are exclusively made of silk-like proteins called âsuckerinsâ, which assemble into nanoconfined ÎČ-sheet reinforced supramolecular networks. In this study, three streamlined strategies for full-length recombinant suckerin protein production and purification were developed. Recombinant suckerin exhibited high solubility and colloidal stability in aqueous-based solvents. In addition, the colloidal suspensions exhibited a concentration-dependent conformational switch, from random coil to ÎČ-sheet enriched structures. Our results demonstrate that recombinant suckerin can be produced in a facile manner in E. coli and processed from mild aqueous solutions into materials enriched in ÎČ-sheets. We suggest that recombinant suckerin-based materials offer potential for a range of biomedical and engineering applications.ASTAR (Agency for Sci., Tech. and Research, Sâpore
Apremilast monotherapy for long-term treatment of active psoriatic arthritis in DMARD-naĂŻve patients
Objectives: apremilast monotherapy was evaluated up to 5âyears in PALACE 4 (fourth PsA Long-term Assessment of Clinical Efficacy study) DMARD-naĂŻve patients with PsA.Methods: patients with active PsA were randomized (1:1:1) to placebo, apremilast 30âmg or apremilast 20âmg twice a day. Placebo patients were rerandomized to apremilast at week 16 or 24. Double-blind apremilast continued to week 52, with a 4-year open-label extension (â€260âweeks of exposure). Analyses through week 260 were based on observed data.Results: a total of 527 patients were treated. Among patients randomized to apremilast 30âmg at baseline, 45.5% completed week 260. At study end, 24.8% reported conventional synthetic DMARD or steroid use for any reason. At week 260, 65.8%/39.0%/20.3% of apremilast 30âmg patients achieved ACR20/ACR50/ACR70 responses, respectively. PsA sign and symptom improvements were sustained up to week 260 with continued treatment, including reductions in swollen (84.8%) and tender (76.4%) joint counts. Among apremilast 30âmg patients with baseline enthesitis or dactylitis, 71.2% achieved a Maastricht Ankylosing Spondylitis Enthesitis Score of 0 and 95.1% achieved a dactylitis count of 0. Over 50% of patients achieved a HAQ Disability Index minimal clinically important difference (â„0.35). In patients with â„3% baseline psoriasis-involved body surface area, 60.3% and 47.6% achieved â„50% and â„75% improvement in Psoriasis Area and Severity Index scores, respectively. Patients continuing apremilast 20âmg also demonstrated consistent, sustained improvements. The most common adverse events were diarrhoea, nausea, headache, upper respiratory tract infection and nasopharyngitis. No new safety concerns were observed long term.Conclusions: apremilast led to sustained PsA efficacy up to 260âweeks and was well tolerated
Apremilast monotherapy for long-term treatment of active psoriatic arthritis in DMARD-naive patients
Objectives: Apremilast monotherapy was evaluated up to 5 years in PALACE 4 DMARD-naive patients with PsA.
Methods: Patients with active PsA were randomized (1:1:1) to placebo, apremilast 30 mg or apremilast 20 mg twice daily. Placebo patients were rerandomized to apremilast at week 16 or 24. Double-blind apremilast continued to week 52, with a 4-year open-label extension (â€260 weeks of exposure). Analyses through week 260 were based on observed data.
Results: 527 patients were treated. Among patients randomized to apremilast 30 mg at baseline, 45.5% completed week 260. At study end, 24.8% reported csDMARD or steroid use for any reason. At week 260, 65.8%/39.0%/20.3% of apremilast 30 mg patients achieved ACR20/ACR50/ACR70 responses, respectively. PsA sign/symptom improvements were sustained up to week 260 with continued treatment, including reductions in swollen (84.8%) and tender (76.4%) joint counts. Among apremilast 30 mg patients with baseline enthesitis or dactylitis, 71.2% achieved a Maastricht Ankylosing Spondylitis Enthesitis Score of 0 and 95.1% achieved a dactylitis count of 0, respectively. Over 50% of patients achieved a HAQ-DI minimal clinically important difference (â„0.35). In patients with â„3% baseline psoriasis-involved body surface area, 60.3% and 47.6% achieved â„50% and â„75% improvement in Psoriasis Area and Severity Index scores, respectively. Patients continuing apremilast 20 mg also demonstrated consistent, sustained improvements. The most common adverse events were diarrhoea, nausea, headache, upper respiratory tract infection and nasopharyngitis. No new safety concerns were observed long term.
Conclusions: Apremilast led to sustained PsA efficacy up to 260 weeks and was well tolerated.
Trial registration: ClinicalTrials.gov (http://clinicaltrials.gov), NCT01307423
Multi-scale thermal stability of a hard thermoplastic protein-based material
Although thermoplastic materials are mostly derived from petro-chemicals, it would be highly desirable, from a sustainability perspective, to produce them instead from renewable biopolymers. Unfortunately, biopolymers exhibiting thermoplastic behaviour and which preserve their mechanical properties post processing are essentially non-existent. The robust sucker ring teeth (SRT) from squid and cuttlefish are one notable exception of thermoplastic biopolymers. Here we describe thermoplastic processing of squid SRT via hot extrusion of fibres, demonstrating the potential suitability of these materials for large-scale thermal forming. Using high-resolution in situ X-ray diffraction and vibrational spectroscopy, we elucidate the molecular and nanoscale features responsible for this behaviour and show that SRT consist of semi-crystalline polymers, whereby heat-resistant, nanocrystalline ÎČ-sheets embedded within an amorphous matrix are organized into a hexagonally packed nanofibrillar lattice. This study provides key insights for the molecular design of biomimetic protein- and peptide-based thermoplastic structural biopolymers with potential biomedical and 3D printing applications
Nanoconfined ÎČâSheets Mechanically Reinforce the Supra-Biomolecular Network of Robust Squid Sucker Ring Teeth
The predatory efficiency of squid and cuttlefish (superorder Decapodiformes) is enhanced by robust Sucker Ring Teeth (SRT) that perform grappling functions during prey capture. Here, we show that SRT are composed entirely of related structural âsuckerinâ proteins whose modular designs enable the formation of nanoconfined ÎČ-sheet-reinforced polymer networks. Thirty-seven previously undiscovered suckerins were identified from transcriptomes assembled from three distantly related decapodiform cephalopods. Similarity in modular sequence design and exonâintron architecture suggests that suckerins are encoded by a multigene family. Phylogenetic analysis supports this view, revealing that suckerin genes originated in a common ancestor âŒ350 MYa and indicating that nanoconfined ÎČ-sheet reinforcement is an ancient strategy to create robust bulk biomaterials. X-ray diffraction, nanomechanical, and micro-Raman spectroscopy measurements confirm that the modular design of the suckerins facilitates the formation of ÎČ-sheets of precise nanoscale dimensions and enables their assembly into structurally robust supramolecular networks stabilized by cooperative hydrogen bonding. The suckerin gene family has likely played a key role in the evolutionary success of decapodiform cephalopods and provides a large molecular toolbox for biomimetic materials engineering
Biomimetic Production of Silk-Like Recombinant Squid Sucker Ring Teeth Proteins
The
sucker ring teeth (SRT) of Humboldt squid exhibit mechanical
properties that rival those of robust engineered synthetic polymers.
Remarkably, these properties are achieved without a mineral phase
or covalent cross-links. Instead, SRT are exclusively made of silk-like
proteins called âsuckerinsâ, which assemble into nanoconfined
ÎČ-sheet reinforced supramolecular networks. In this study, three
streamlined strategies for full-length recombinant suckerin protein
production and purification were developed. Recombinant suckerin exhibited
high solubility and colloidal stability in aqueous-based solvents.
In addition, the colloidal suspensions exhibited a concentration-dependent
conformational switch, from random coil to ÎČ-sheet enriched
structures. Our results demonstrate that recombinant suckerin can
be produced in a facile manner in E. coli and processed from mild aqueous solutions into materials enriched
in ÎČ-sheets. We suggest that recombinant suckerin-based materials
offer potential for a range of biomedical and engineering applications
The MUMBA campaign: measurements of urban, marine and biogenic air
The Measurements of Urban, Marine and Biogenic Air (MUMBA) campaign took place in Wollongong, New South Wales (a small coastal city approximately 80 km south of Sydney, Australia) from 21 December 2012 to 15 February 2013. Like many Australian cities, Wollongong is surrounded by dense eucalyptus forest, so the urban airshed is heavily influenced by biogenic emissions. Instruments were deployed during MUMBA to measure the gaseous and aerosol composition of the atmosphere with the aim of providing a detailed characterisation of the complex environment of the ocean-forest-urban interface that could be used to test the skill of atmospheric models. The gases measured included ozone, oxides of nitrogen, carbon monoxide, carbon dioxide, methane and many of the most abundant volatile organic compounds. The aerosol characterisation included total particle counts above 3 nm, total cloud condensation nuclei counts, mass concentration, number concentration size distribution, aerosol chemical analyses and elemental analysis. The campaign captured varied meteorological conditions, including two extreme heat events, providing a potentially valuable test for models of future air quality in a warmer climate. There was also an episode when the site sampled clean marine air for many hours, providing a useful additional measure of the background concentrations of these trace gases within this poorly sampled region of the globe. In this paper we describe the campaign, the meteorology and the resulting observations of atmospheric composition in general terms in order to equip the reader with a sufficient understanding of the Wollongong regional influences to use the MUMBA datasets as a case study for testing a chemical transport model. The data are available from PANGAEA (http: //doi.pangaea.de/10.1594/PANGAEA.871982)