Force regulated conformational change of integrin αVβ3

Integrins mediate cell adhesion to extracellular matrix and transduce signals bidirectionally across the membrane. Integrin αVβ3 has been shown to play an essential role in tumor metastasis, angiogenesis, hemostasis and phagocytosis. Integrins can take several conformations, including the bent and e...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Matrix biology 2017-07, Vol.60-61, p.70-85
Hauptverfasser: Chen, Yunfeng, Lee, Hyunjung, Tong, Haibin, Schwartz, Martin, Zhu, Cheng
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 85
container_issue
container_start_page 70
container_title Matrix biology
container_volume 60-61
creator Chen, Yunfeng
Lee, Hyunjung
Tong, Haibin
Schwartz, Martin
Zhu, Cheng
description Integrins mediate cell adhesion to extracellular matrix and transduce signals bidirectionally across the membrane. Integrin αVβ3 has been shown to play an essential role in tumor metastasis, angiogenesis, hemostasis and phagocytosis. Integrins can take several conformations, including the bent and extended conformations of the ectodomain, which regulate integrin functions. Using a biomembrane force probe, we characterized the bending and unbending conformational changes of single αVβ3 integrins on living cell surfaces in real-time. We measured the probabilities of conformational changes, rates and speeds of conformational transitions, and the dynamic equilibrium between the two conformations, which were regulated by tensile force, dependent on the ligand, and altered by point mutations. These findings provide insights into how αVβ3 acts as a molecular machine and how its physiological function and molecular structure are coupled at the single‐molecule level. •We characterized the bending and unbending conformational changes of a single integrin αVβ3 molecule on a living cell surface in real-time.•The bending and unbending conformational changes are regulated by tensile force, dependent on the ligand, and altered by point mutations.•Our findings provide insights into how the physiological functions and molecular structure of αVβ3 are coupled at the single molecule level.
doi_str_mv 10.1016/j.matbio.2016.07.002
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5237428</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0945053X16301585</els_id><sourcerecordid>1826723762</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3552-e652b53ed2e69d5c6d085d134e81d03a19d434fcea219424847bbc6a1fd7a95d3</originalsourceid><addsrcrecordid>eNp9kM9KAzEQh4MoWqtv4GGPXnbN393sRZBiVRC8qHgL2WS2TdkmmmwFH0sfpM_klhbFi6dhmB_fzHwInRFcEEzKi0Wx1H3jQkGHrsBVgTHdQyMiyjonEtN9NMI1FzkW7OUIHae0wBhzXslDdEQrThmT9QjJaYgGsgizVad7sJkJvg1xQLvgdZeZufYzyEKbOd_DLDqfrT-f11_sBB20uktwuqtj9DS9fpzc5vcPN3eTq_vcMCFoDqWgjWBgKZS1Faa0WApLGAdJLGaa1JYz3hrQlNSccsmrpjGlJq2tdC0sG6PLLfd11SzBGvB91J16jW6p44cK2qm_E-_mahbelaBs-FIOgPMdIIa3FaReLV0y0HXaQ1glRSQtqyFb0iHKt1ETQ0oR2p81BKuNdLVQW-lqI13hSg3Sf0-EwcO7g6iSceANWBfB9MoG9z_gG3KBjRU</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1826723762</pqid></control><display><type>article</type><title>Force regulated conformational change of integrin αVβ3</title><source>Access via ScienceDirect (Elsevier)</source><creator>Chen, Yunfeng ; Lee, Hyunjung ; Tong, Haibin ; Schwartz, Martin ; Zhu, Cheng</creator><creatorcontrib>Chen, Yunfeng ; Lee, Hyunjung ; Tong, Haibin ; Schwartz, Martin ; Zhu, Cheng</creatorcontrib><description>Integrins mediate cell adhesion to extracellular matrix and transduce signals bidirectionally across the membrane. Integrin αVβ3 has been shown to play an essential role in tumor metastasis, angiogenesis, hemostasis and phagocytosis. Integrins can take several conformations, including the bent and extended conformations of the ectodomain, which regulate integrin functions. Using a biomembrane force probe, we characterized the bending and unbending conformational changes of single αVβ3 integrins on living cell surfaces in real-time. We measured the probabilities of conformational changes, rates and speeds of conformational transitions, and the dynamic equilibrium between the two conformations, which were regulated by tensile force, dependent on the ligand, and altered by point mutations. These findings provide insights into how αVβ3 acts as a molecular machine and how its physiological function and molecular structure are coupled at the single‐molecule level. •We characterized the bending and unbending conformational changes of a single integrin αVβ3 molecule on a living cell surface in real-time.•The bending and unbending conformational changes are regulated by tensile force, dependent on the ligand, and altered by point mutations.•Our findings provide insights into how the physiological functions and molecular structure of αVβ3 are coupled at the single molecule level.</description><identifier>ISSN: 0945-053X</identifier><identifier>EISSN: 1569-1802</identifier><identifier>DOI: 10.1016/j.matbio.2016.07.002</identifier><identifier>PMID: 27423389</identifier><language>eng</language><publisher>Elsevier B.V</publisher><subject>Binding kinetics ; Biomechanics ; Force regulation ; Integrin conformational change ; Integrin αVβ3</subject><ispartof>Matrix biology, 2017-07, Vol.60-61, p.70-85</ispartof><rights>2016 Elsevier B.V.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3552-e652b53ed2e69d5c6d085d134e81d03a19d434fcea219424847bbc6a1fd7a95d3</citedby><cites>FETCH-LOGICAL-c3552-e652b53ed2e69d5c6d085d134e81d03a19d434fcea219424847bbc6a1fd7a95d3</cites><orcidid>0000-0002-1718-565X ; 0000-0001-7618-107X ; 0000-0002-2071-1243</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.matbio.2016.07.002$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,315,781,785,886,3551,27926,27927,45997</link.rule.ids></links><search><creatorcontrib>Chen, Yunfeng</creatorcontrib><creatorcontrib>Lee, Hyunjung</creatorcontrib><creatorcontrib>Tong, Haibin</creatorcontrib><creatorcontrib>Schwartz, Martin</creatorcontrib><creatorcontrib>Zhu, Cheng</creatorcontrib><title>Force regulated conformational change of integrin αVβ3</title><title>Matrix biology</title><description>Integrins mediate cell adhesion to extracellular matrix and transduce signals bidirectionally across the membrane. Integrin αVβ3 has been shown to play an essential role in tumor metastasis, angiogenesis, hemostasis and phagocytosis. Integrins can take several conformations, including the bent and extended conformations of the ectodomain, which regulate integrin functions. Using a biomembrane force probe, we characterized the bending and unbending conformational changes of single αVβ3 integrins on living cell surfaces in real-time. We measured the probabilities of conformational changes, rates and speeds of conformational transitions, and the dynamic equilibrium between the two conformations, which were regulated by tensile force, dependent on the ligand, and altered by point mutations. These findings provide insights into how αVβ3 acts as a molecular machine and how its physiological function and molecular structure are coupled at the single‐molecule level. •We characterized the bending and unbending conformational changes of a single integrin αVβ3 molecule on a living cell surface in real-time.•The bending and unbending conformational changes are regulated by tensile force, dependent on the ligand, and altered by point mutations.•Our findings provide insights into how the physiological functions and molecular structure of αVβ3 are coupled at the single molecule level.</description><subject>Binding kinetics</subject><subject>Biomechanics</subject><subject>Force regulation</subject><subject>Integrin conformational change</subject><subject>Integrin αVβ3</subject><issn>0945-053X</issn><issn>1569-1802</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNp9kM9KAzEQh4MoWqtv4GGPXnbN393sRZBiVRC8qHgL2WS2TdkmmmwFH0sfpM_klhbFi6dhmB_fzHwInRFcEEzKi0Wx1H3jQkGHrsBVgTHdQyMiyjonEtN9NMI1FzkW7OUIHae0wBhzXslDdEQrThmT9QjJaYgGsgizVad7sJkJvg1xQLvgdZeZufYzyEKbOd_DLDqfrT-f11_sBB20uktwuqtj9DS9fpzc5vcPN3eTq_vcMCFoDqWgjWBgKZS1Faa0WApLGAdJLGaa1JYz3hrQlNSccsmrpjGlJq2tdC0sG6PLLfd11SzBGvB91J16jW6p44cK2qm_E-_mahbelaBs-FIOgPMdIIa3FaReLV0y0HXaQ1glRSQtqyFb0iHKt1ETQ0oR2p81BKuNdLVQW-lqI13hSg3Sf0-EwcO7g6iSceANWBfB9MoG9z_gG3KBjRU</recordid><startdate>20170701</startdate><enddate>20170701</enddate><creator>Chen, Yunfeng</creator><creator>Lee, Hyunjung</creator><creator>Tong, Haibin</creator><creator>Schwartz, Martin</creator><creator>Zhu, Cheng</creator><general>Elsevier B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1718-565X</orcidid><orcidid>https://orcid.org/0000-0001-7618-107X</orcidid><orcidid>https://orcid.org/0000-0002-2071-1243</orcidid></search><sort><creationdate>20170701</creationdate><title>Force regulated conformational change of integrin αVβ3</title><author>Chen, Yunfeng ; Lee, Hyunjung ; Tong, Haibin ; Schwartz, Martin ; Zhu, Cheng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3552-e652b53ed2e69d5c6d085d134e81d03a19d434fcea219424847bbc6a1fd7a95d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Binding kinetics</topic><topic>Biomechanics</topic><topic>Force regulation</topic><topic>Integrin conformational change</topic><topic>Integrin αVβ3</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Yunfeng</creatorcontrib><creatorcontrib>Lee, Hyunjung</creatorcontrib><creatorcontrib>Tong, Haibin</creatorcontrib><creatorcontrib>Schwartz, Martin</creatorcontrib><creatorcontrib>Zhu, Cheng</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Matrix biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Yunfeng</au><au>Lee, Hyunjung</au><au>Tong, Haibin</au><au>Schwartz, Martin</au><au>Zhu, Cheng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Force regulated conformational change of integrin αVβ3</atitle><jtitle>Matrix biology</jtitle><date>2017-07-01</date><risdate>2017</risdate><volume>60-61</volume><spage>70</spage><epage>85</epage><pages>70-85</pages><issn>0945-053X</issn><eissn>1569-1802</eissn><abstract>Integrins mediate cell adhesion to extracellular matrix and transduce signals bidirectionally across the membrane. Integrin αVβ3 has been shown to play an essential role in tumor metastasis, angiogenesis, hemostasis and phagocytosis. Integrins can take several conformations, including the bent and extended conformations of the ectodomain, which regulate integrin functions. Using a biomembrane force probe, we characterized the bending and unbending conformational changes of single αVβ3 integrins on living cell surfaces in real-time. We measured the probabilities of conformational changes, rates and speeds of conformational transitions, and the dynamic equilibrium between the two conformations, which were regulated by tensile force, dependent on the ligand, and altered by point mutations. These findings provide insights into how αVβ3 acts as a molecular machine and how its physiological function and molecular structure are coupled at the single‐molecule level. •We characterized the bending and unbending conformational changes of a single integrin αVβ3 molecule on a living cell surface in real-time.•The bending and unbending conformational changes are regulated by tensile force, dependent on the ligand, and altered by point mutations.•Our findings provide insights into how the physiological functions and molecular structure of αVβ3 are coupled at the single molecule level.</abstract><pub>Elsevier B.V</pub><pmid>27423389</pmid><doi>10.1016/j.matbio.2016.07.002</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-1718-565X</orcidid><orcidid>https://orcid.org/0000-0001-7618-107X</orcidid><orcidid>https://orcid.org/0000-0002-2071-1243</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0945-053X
ispartof Matrix biology, 2017-07, Vol.60-61, p.70-85
issn 0945-053X
1569-1802
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5237428
source Access via ScienceDirect (Elsevier)
subjects Binding kinetics
Biomechanics
Force regulation
Integrin conformational change
Integrin αVβ3
title Force regulated conformational change of integrin αVβ3
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-17T15%3A47%3A31IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Force%20regulated%20conformational%20change%20of%20integrin%20%CE%B1V%CE%B23&rft.jtitle=Matrix%20biology&rft.au=Chen,%20Yunfeng&rft.date=2017-07-01&rft.volume=60-61&rft.spage=70&rft.epage=85&rft.pages=70-85&rft.issn=0945-053X&rft.eissn=1569-1802&rft_id=info:doi/10.1016/j.matbio.2016.07.002&rft_dat=%3Cproquest_pubme%3E1826723762%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1826723762&rft_id=info:pmid/27423389&rft_els_id=S0945053X16301585&rfr_iscdi=true