Biology subjects

Scurr, D. J.

Publications and source records attributed to Scurr, D. J..

5 recordsLinked to original sources

bioRxiv2025

Molecular biointerface characterisation for an implanted medical device using cryogenic orbitrap secondary ion mass spectrometry (Cryo-OrbiSIMS)

Implanted medical devices often fail due to foreign body reaction (FBR), a process still not fully understood. This work presents a new depth profiling approach to provide insight into the spatial metabolomics of the biointerface of implants, revealing biomolecular strata representative of the host response. This study examines silicone rubber poly(dimethyl siloxane) catheters implanted in mice for 1 and 28 days. Cryo-OrbiSIMS was used in combination with ToF-SIMS to identify metabolite profiles from the biological deposit found on the implants after removal from the tissue which were previously unattainable using tissue sectioning. Machine learning and statistical analysis of the profiles were used to help identify early biointerface responses to the implant, including at 1 day of implantation the observation of elevated sugars and itaconate an immunomodulatory metabolite that modulates FBR. At day 28 inflammation associated markers were observed such as urate and palmitic acid (FA 16:0). Depth profiling revealed two distinct molecular layers in the deposits: amino acids, and nucleic acids were preferentially seen towards the host tissue, consistent with the observation of a cell monolayer in the tissue sections, whereas certain lipids and fatty acids where either at the catheter-deposit interface or towards the host tissue after 28 days. The stratification was less well developed at 1-day implantation, but common lipids were seen at the deposit-implant interface across both time points. These insights advance understanding of FBR and support the development of improved implant materials.

bioinformatics↗

bioRxiv2024

Molecular surface chemistry defines nematode development, identity and behaviour

ABSTRACT/SUMMARYChemical signalling facilitates organismal communication and coordinates physiological and behavioural processes. In nematodes, signalling has predominantly focused on secreted molecules leaving the surfaces communicative potential unexplored. By utilising 3D-OrbiSIMS, an advanced surface-sensitive mass spectrometry method, we directly characterised the molecular composition of the outermost regions (50 nm in depth) of Caenorhabditis elegans and Pristionchus pacificus to improve the understanding of surface-mediated chemical communication. We found that nematode surfaces consist of a lipid-dominated landscape (> 81 % C. elegans and > 69 % P. pacificus of all surveyed chemistries) with distinct compositions, which enrich in granularity and complexity through development. The surface-anchored lipids are also species-specific, reflecting evolutionary and ecological adaptations to their environmental niches. By exploring the effect of mutations on lipid production we found the peroxisomal fatty acid {beta}-oxidation component daf-22 is essential for defining the surface molecular fingerprint. This pathway is conserved across species in producing distinct chemical profiles, indicating its fundamental role in lipid metabolism and for maintaining surface integrity and function. Furthermore, we discovered that variations in surface-anchored lipids of C. elegans daf-22 larvae contribute to significantly increased susceptibility to predation by P. pacificus. Therefore, our findings reveal that the nematode surface is not just a passive boundary but a dynamic signalling platform with evolved, species-specific signatures. These molecular mechanisms are pivotal in shaping identity and communication strategies, providing new insights into the evolutionary and ecological dynamics of chemical signalling across organisms. HIGHLIGHTSO_LINematode surfaces are lipid-rich, changing with development. C_LIO_LISurface lipids are species-specific, reflecting adaptations. C_LIO_LIThe daf-22 gene is key in shaping the surface lipid profile. C_LIO_LISurface lipids mediate predator-prey interactions in nematodes. C_LI

systems biology↗

bioRxiv2023

Spatially resolved molecular analysis of host response to medical device implantation using the 3D OrbiSIMS

A key goal for implanted medical devices is that they do not elicit a detrimental immune response. Macrophages play critical roles in modulation of the host immune response and are the major cells responsible for persistent inflammatory reactions to implanted biomaterials. We investigate two novel immune-instructive polymers that stimulate pro- or anti-inflammatory responses from macrophages in vitro. These also modulate in vivo foreign body responses (FBR) when implanted subcutaneously in mice as coatings on biomedical grade silicone rubber. The tissue surrounding the implant is mechanically sectioned and imaged to assess the response of the polymers compared to silicone rubber. Immunofluorescent staining reveals responses consistent with pro- or anti-inflammatory responses previously described for these polymers. We apply 3D OrbiSIMS analysis to provide spatial analysis of the metabolite signature in the tissue surrounding the implant for the first time, providing molecular histology insight into the metabolite response in the host tissue. For the pro-inflammatory coating, monoacylglycerols (MG) and diacylglycerols (DG) are observed at increased intensity, while for the anti-inflammatory coating the number of phospholipid species detected decrease and pyridine and pyrimidine levels were elevated. These findings link to observations of small molecule signature from single cell studies of M2 macrophages in vitro where cell and tissue ion intensities were found to correlate suggesting potential for prediction. This illustrates the power of metabolite characterization by the 3D OrbiSIMS to gain insight into the mechanism of bio-instructive materials as medical devices and to inform on the FBR to biomaterials.

bioengineering↗

bioRxiv2020

Metabolic profiles as putative predictors of relapse in pediatric brain tumour using direct surface and imaging mass spectrometry

We present here a novel surface mass spectrometry strategy to perform untargeted metabolite profiling of formalin-fixed paraffin-embedded (FFPE) pediatric ependymoma archives. Sequential Orbitrap secondary ion mass spectrometry (3D OrbiSIMS) and liquid extraction surface analysis-tandem MS (LESA-MS/MS) permitted the detection of 887 metabolites (163 chemical classes) from pediatric ependymoma tumor tissue microarrays (diameter <1 mm; thickness: 4 m). From these 163 classes, 60 classes were detected with both techniques, whilst LESA-MS/MS and 3D OrbiSIMS individually allowed the detection of another 83 and 20 unique metabolite classes, respectively. Through data fusion and multivariate analysis, we were able to identify key metabolites and corresponding pathways predictive of tumor relapse which were retrospectively confirmed using gene expression analysis with publicly available data. Altogether, this sequential mass spectrometry strategy has shown to be a versatile tool to perform high throughput metabolite profiling on sample-limited tissue archives. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=91 SRC="FIGDIR/small/182071v3_ufig1.gif" ALT="Figure 1"> View larger version (11K): org.highwire.dtl.DTLVardef@1f9c850org.highwire.dtl.DTLVardef@1ce0568org.highwire.dtl.DTLVardef@c5023borg.highwire.dtl.DTLVardef@15ad6e_HPS_FORMAT_FIGEXP M_FIG For Table of Contents Only C_FIG

cancer biology↗

bioRxiv2019

In situ protein identification and mapping using secondary ion mass spectrometry

Protein characterisation at surfaces currently requires digestion prior to either liquid extraction of the protein for mass spectrometry analysis or in situ matrix-assisted desorption/ionisation. Here, we show that direct assignment of individual proteins and mixtures at surfaces can be achieved by employing secondary ion mass spectrometry (SIMS) with gas cluster ion beam (GCIB) bombardment and an Orbitrap analyser. Potential applications of the method are illustrated by demonstrating imaging of a protein film masked by a gold grid and the analysis of a protein monolayer biochip.

biochemistry↗