Imperial College London

Dr Nick Brooks

Faculty of Natural SciencesDepartment of Chemistry

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 2677n.brooks Website

 
 
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Location

 

207JMolecular Sciences Research HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Holme:2018:10.1021/acsnano.8b03308,
author = {Holme, MN and Rana, S and Barriga, H and Kauscher, U and Brooks, NJ and Stevens, MM},
doi = {10.1021/acsnano.8b03308},
journal = {ACS Nano},
pages = {8197--8207},
title = {A robust liposomal platform for direct colorimetric detection of sphingomyelinase enzyme and inhibitors},
url = {http://dx.doi.org/10.1021/acsnano.8b03308},
volume = {12},
year = {2018}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - The enzyme sphingomyelinase (SMase) is an important biomarker for several diseases such as Niemann Pick’s, atherosclerosis, multiple sclerosis, and HIV. We present a two-component colorimetric SMase activity assay that is more sensitive and much faster than currently available commercial assays. Herein, SMase-triggered release of cysteine from a sphingomyelin (SM)-based liposome formulation with 60 mol % cholesterol causes gold nanoparticle (AuNP) aggregation, enabling colorimetric detection of SMase activities as low as 0.02 mU/mL, corresponding to 1.4 pM concentration. While the lipid composition offers a stable, nonleaky liposome platform with minimal background signal, high specificity toward SMase avoids cross-reactivity of other similar phospholipases. Notably, use of an SM-based liposome formulation accurately mimics the natural in vivo substrate: the cell membrane. We studied the physical rearrangement process of the lipid membrane during SMase-mediated hydrolysis of SM to ceramide using small- and wide-angle X-ray scattering. A change in lipid phase from a liquid to gel state bilayer with increasing concentration of ceramide accounts for the observed increase in membrane permeability and consequent release of encapsulated cysteine. We further demonstrated the effectiveness of the sensor in colorimetric screening of small-molecule drug candidates, paving the way for the identification of novel SMase inhibitors in minutes. Taken together, the simplicity, speed, sensitivity, and naked-eye readout of this assay offer huge potential in point-of-care diagnostics and high-throughput drug screening.
AU - Holme,MN
AU - Rana,S
AU - Barriga,H
AU - Kauscher,U
AU - Brooks,NJ
AU - Stevens,MM
DO - 10.1021/acsnano.8b03308
EP - 8207
PY - 2018///
SN - 1936-0851
SP - 8197
TI - A robust liposomal platform for direct colorimetric detection of sphingomyelinase enzyme and inhibitors
T2 - ACS Nano
UR - http://dx.doi.org/10.1021/acsnano.8b03308
UR - http://hdl.handle.net/10044/1/62829
VL - 12
ER -