Optical Nanosensing of Lipid Accumulation due to Enzyme Inhibition in Live Cells
Drugs that influence enzymes of lipid metabolism can cause pathological accumulation of lipids in animal cells. Here, gold nanoparticles, acting as nanosensors that deliver surface-enhanced Raman scattering (SERS) spectra from living cells provide molecular evidence of lipid accumulation in lysosome...
Gespeichert in:
Veröffentlicht in: | ACS nano 2019-08, Vol.13 (8), p.9363-9375 |
---|---|
Hauptverfasser: | , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 9375 |
---|---|
container_issue | 8 |
container_start_page | 9363 |
container_title | ACS nano |
container_volume | 13 |
creator | Živanović, Vesna Seifert, Stephan Drescher, Daniela Schrade, Petra Werner, Stephan Guttmann, Peter Szekeres, Gergo Peter Bachmann, Sebastian Schneider, Gerd Arenz, Christoph Kneipp, Janina |
description | Drugs that influence enzymes of lipid metabolism can cause pathological accumulation of lipids in animal cells. Here, gold nanoparticles, acting as nanosensors that deliver surface-enhanced Raman scattering (SERS) spectra from living cells provide molecular evidence of lipid accumulation in lysosomes after treatment of cultured cells with the three tricyclic antidepressants (TCA) desipramine, amitryptiline, and imipramine. The vibrational spectra elucidate to great detail and with very high sensitivity the composition of the drug-induced lipid accumulations, also observed in fixed samples by electron microscopy and X-ray nanotomography. The nanoprobes show that mostly sphingomyelin is accumulated in the lysosomes but also other lipids, in particular, cholesterol. The observation of sphingomyelin accumulation supports the impairment of the enzyme acid sphingomyelinase. The SERS data were analyzed by random forest based approaches, in particular, by minimal depth variable selection and surrogate minimal depth (SMD), shown here to be particularly useful machine learning tools for the analysis of the lipid signals that contribute only weakly to SERS spectra of cells. SMD is used for the identification of molecular colocalization and interactions of the drug molecules with lipid membranes and for discriminating between the biochemical effects of the three different TCA molecules, in agreement with their different activity. The spectra also indicate that the protein composition is significantly changed in cells treated with the drugs. |
doi_str_mv | 10.1021/acsnano.9b04001 |
format | Article |
fullrecord | <record><control><sourceid>acs_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1021_acsnano_9b04001</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>b105827871</sourcerecordid><originalsourceid>FETCH-LOGICAL-a333t-acfd5f4b5ec40fe704ecc9e1ec3d316a9b7eb6014d6bf27c55ce20a6a48907df3</originalsourceid><addsrcrecordid>eNp1kM9LwzAUx4Mobk7P3iR36UyWNG2OY0wdDOdBwVvJjxfNaNPStML8661u7ubpPXif7xfeB6FrSqaUzOidMjGoUE-lJpwQeoLGVDKRkFy8nR73lI7QRYxbQtIsz8Q5GjHKKJe5HKPnTdN5o0r8NNRECNGHd1w7vPaNt3huTF_1pep8HbDtAXc1XoavXQV4FT689r8HHwb8E_ACyjJeojOnyghXhzlBr_fLl8Vjst48rBbzdaIYY12ijLOp4zoFw4mDjHAwRgIFwyyjQkmdgRaEciu0m2UmTQ3MiBKK55Jk1rEJutv3mraOsQVXNK2vVLsrKCl-3BQHN8XBzZC42SeaXldgj_yfjAG43QNDstjWfRuGB_6t-waxkHEZ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Optical Nanosensing of Lipid Accumulation due to Enzyme Inhibition in Live Cells</title><source>American Chemical Society Journals</source><creator>Živanović, Vesna ; Seifert, Stephan ; Drescher, Daniela ; Schrade, Petra ; Werner, Stephan ; Guttmann, Peter ; Szekeres, Gergo Peter ; Bachmann, Sebastian ; Schneider, Gerd ; Arenz, Christoph ; Kneipp, Janina</creator><creatorcontrib>Živanović, Vesna ; Seifert, Stephan ; Drescher, Daniela ; Schrade, Petra ; Werner, Stephan ; Guttmann, Peter ; Szekeres, Gergo Peter ; Bachmann, Sebastian ; Schneider, Gerd ; Arenz, Christoph ; Kneipp, Janina</creatorcontrib><description>Drugs that influence enzymes of lipid metabolism can cause pathological accumulation of lipids in animal cells. Here, gold nanoparticles, acting as nanosensors that deliver surface-enhanced Raman scattering (SERS) spectra from living cells provide molecular evidence of lipid accumulation in lysosomes after treatment of cultured cells with the three tricyclic antidepressants (TCA) desipramine, amitryptiline, and imipramine. The vibrational spectra elucidate to great detail and with very high sensitivity the composition of the drug-induced lipid accumulations, also observed in fixed samples by electron microscopy and X-ray nanotomography. The nanoprobes show that mostly sphingomyelin is accumulated in the lysosomes but also other lipids, in particular, cholesterol. The observation of sphingomyelin accumulation supports the impairment of the enzyme acid sphingomyelinase. The SERS data were analyzed by random forest based approaches, in particular, by minimal depth variable selection and surrogate minimal depth (SMD), shown here to be particularly useful machine learning tools for the analysis of the lipid signals that contribute only weakly to SERS spectra of cells. SMD is used for the identification of molecular colocalization and interactions of the drug molecules with lipid membranes and for discriminating between the biochemical effects of the three different TCA molecules, in agreement with their different activity. The spectra also indicate that the protein composition is significantly changed in cells treated with the drugs.</description><identifier>ISSN: 1936-0851</identifier><identifier>EISSN: 1936-086X</identifier><identifier>DOI: 10.1021/acsnano.9b04001</identifier><identifier>PMID: 31314989</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><ispartof>ACS nano, 2019-08, Vol.13 (8), p.9363-9375</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a333t-acfd5f4b5ec40fe704ecc9e1ec3d316a9b7eb6014d6bf27c55ce20a6a48907df3</citedby><cites>FETCH-LOGICAL-a333t-acfd5f4b5ec40fe704ecc9e1ec3d316a9b7eb6014d6bf27c55ce20a6a48907df3</cites><orcidid>0000-0002-0534-238X ; 0000-0001-8542-6331</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acsnano.9b04001$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acsnano.9b04001$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31314989$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Živanović, Vesna</creatorcontrib><creatorcontrib>Seifert, Stephan</creatorcontrib><creatorcontrib>Drescher, Daniela</creatorcontrib><creatorcontrib>Schrade, Petra</creatorcontrib><creatorcontrib>Werner, Stephan</creatorcontrib><creatorcontrib>Guttmann, Peter</creatorcontrib><creatorcontrib>Szekeres, Gergo Peter</creatorcontrib><creatorcontrib>Bachmann, Sebastian</creatorcontrib><creatorcontrib>Schneider, Gerd</creatorcontrib><creatorcontrib>Arenz, Christoph</creatorcontrib><creatorcontrib>Kneipp, Janina</creatorcontrib><title>Optical Nanosensing of Lipid Accumulation due to Enzyme Inhibition in Live Cells</title><title>ACS nano</title><addtitle>ACS Nano</addtitle><description>Drugs that influence enzymes of lipid metabolism can cause pathological accumulation of lipids in animal cells. Here, gold nanoparticles, acting as nanosensors that deliver surface-enhanced Raman scattering (SERS) spectra from living cells provide molecular evidence of lipid accumulation in lysosomes after treatment of cultured cells with the three tricyclic antidepressants (TCA) desipramine, amitryptiline, and imipramine. The vibrational spectra elucidate to great detail and with very high sensitivity the composition of the drug-induced lipid accumulations, also observed in fixed samples by electron microscopy and X-ray nanotomography. The nanoprobes show that mostly sphingomyelin is accumulated in the lysosomes but also other lipids, in particular, cholesterol. The observation of sphingomyelin accumulation supports the impairment of the enzyme acid sphingomyelinase. The SERS data were analyzed by random forest based approaches, in particular, by minimal depth variable selection and surrogate minimal depth (SMD), shown here to be particularly useful machine learning tools for the analysis of the lipid signals that contribute only weakly to SERS spectra of cells. SMD is used for the identification of molecular colocalization and interactions of the drug molecules with lipid membranes and for discriminating between the biochemical effects of the three different TCA molecules, in agreement with their different activity. The spectra also indicate that the protein composition is significantly changed in cells treated with the drugs.</description><issn>1936-0851</issn><issn>1936-086X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp1kM9LwzAUx4Mobk7P3iR36UyWNG2OY0wdDOdBwVvJjxfNaNPStML8661u7ubpPXif7xfeB6FrSqaUzOidMjGoUE-lJpwQeoLGVDKRkFy8nR73lI7QRYxbQtIsz8Q5GjHKKJe5HKPnTdN5o0r8NNRECNGHd1w7vPaNt3huTF_1pep8HbDtAXc1XoavXQV4FT689r8HHwb8E_ACyjJeojOnyghXhzlBr_fLl8Vjst48rBbzdaIYY12ijLOp4zoFw4mDjHAwRgIFwyyjQkmdgRaEciu0m2UmTQ3MiBKK55Jk1rEJutv3mraOsQVXNK2vVLsrKCl-3BQHN8XBzZC42SeaXldgj_yfjAG43QNDstjWfRuGB_6t-waxkHEZ</recordid><startdate>20190827</startdate><enddate>20190827</enddate><creator>Živanović, Vesna</creator><creator>Seifert, Stephan</creator><creator>Drescher, Daniela</creator><creator>Schrade, Petra</creator><creator>Werner, Stephan</creator><creator>Guttmann, Peter</creator><creator>Szekeres, Gergo Peter</creator><creator>Bachmann, Sebastian</creator><creator>Schneider, Gerd</creator><creator>Arenz, Christoph</creator><creator>Kneipp, Janina</creator><general>American Chemical Society</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0002-0534-238X</orcidid><orcidid>https://orcid.org/0000-0001-8542-6331</orcidid></search><sort><creationdate>20190827</creationdate><title>Optical Nanosensing of Lipid Accumulation due to Enzyme Inhibition in Live Cells</title><author>Živanović, Vesna ; Seifert, Stephan ; Drescher, Daniela ; Schrade, Petra ; Werner, Stephan ; Guttmann, Peter ; Szekeres, Gergo Peter ; Bachmann, Sebastian ; Schneider, Gerd ; Arenz, Christoph ; Kneipp, Janina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a333t-acfd5f4b5ec40fe704ecc9e1ec3d316a9b7eb6014d6bf27c55ce20a6a48907df3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Živanović, Vesna</creatorcontrib><creatorcontrib>Seifert, Stephan</creatorcontrib><creatorcontrib>Drescher, Daniela</creatorcontrib><creatorcontrib>Schrade, Petra</creatorcontrib><creatorcontrib>Werner, Stephan</creatorcontrib><creatorcontrib>Guttmann, Peter</creatorcontrib><creatorcontrib>Szekeres, Gergo Peter</creatorcontrib><creatorcontrib>Bachmann, Sebastian</creatorcontrib><creatorcontrib>Schneider, Gerd</creatorcontrib><creatorcontrib>Arenz, Christoph</creatorcontrib><creatorcontrib>Kneipp, Janina</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><jtitle>ACS nano</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Živanović, Vesna</au><au>Seifert, Stephan</au><au>Drescher, Daniela</au><au>Schrade, Petra</au><au>Werner, Stephan</au><au>Guttmann, Peter</au><au>Szekeres, Gergo Peter</au><au>Bachmann, Sebastian</au><au>Schneider, Gerd</au><au>Arenz, Christoph</au><au>Kneipp, Janina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Optical Nanosensing of Lipid Accumulation due to Enzyme Inhibition in Live Cells</atitle><jtitle>ACS nano</jtitle><addtitle>ACS Nano</addtitle><date>2019-08-27</date><risdate>2019</risdate><volume>13</volume><issue>8</issue><spage>9363</spage><epage>9375</epage><pages>9363-9375</pages><issn>1936-0851</issn><eissn>1936-086X</eissn><abstract>Drugs that influence enzymes of lipid metabolism can cause pathological accumulation of lipids in animal cells. Here, gold nanoparticles, acting as nanosensors that deliver surface-enhanced Raman scattering (SERS) spectra from living cells provide molecular evidence of lipid accumulation in lysosomes after treatment of cultured cells with the three tricyclic antidepressants (TCA) desipramine, amitryptiline, and imipramine. The vibrational spectra elucidate to great detail and with very high sensitivity the composition of the drug-induced lipid accumulations, also observed in fixed samples by electron microscopy and X-ray nanotomography. The nanoprobes show that mostly sphingomyelin is accumulated in the lysosomes but also other lipids, in particular, cholesterol. The observation of sphingomyelin accumulation supports the impairment of the enzyme acid sphingomyelinase. The SERS data were analyzed by random forest based approaches, in particular, by minimal depth variable selection and surrogate minimal depth (SMD), shown here to be particularly useful machine learning tools for the analysis of the lipid signals that contribute only weakly to SERS spectra of cells. SMD is used for the identification of molecular colocalization and interactions of the drug molecules with lipid membranes and for discriminating between the biochemical effects of the three different TCA molecules, in agreement with their different activity. The spectra also indicate that the protein composition is significantly changed in cells treated with the drugs.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>31314989</pmid><doi>10.1021/acsnano.9b04001</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-0534-238X</orcidid><orcidid>https://orcid.org/0000-0001-8542-6331</orcidid></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1936-0851 |
ispartof | ACS nano, 2019-08, Vol.13 (8), p.9363-9375 |
issn | 1936-0851 1936-086X |
language | eng |
recordid | cdi_crossref_primary_10_1021_acsnano_9b04001 |
source | American Chemical Society Journals |
title | Optical Nanosensing of Lipid Accumulation due to Enzyme Inhibition in Live Cells |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T03%3A36%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-acs_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Optical%20Nanosensing%20of%20Lipid%20Accumulation%20due%20to%20Enzyme%20Inhibition%20in%20Live%20Cells&rft.jtitle=ACS%20nano&rft.au=Z%CC%8Civanovic%CC%81,%20Vesna&rft.date=2019-08-27&rft.volume=13&rft.issue=8&rft.spage=9363&rft.epage=9375&rft.pages=9363-9375&rft.issn=1936-0851&rft.eissn=1936-086X&rft_id=info:doi/10.1021/acsnano.9b04001&rft_dat=%3Cacs_cross%3Eb105827871%3C/acs_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/31314989&rfr_iscdi=true |