Leveraging on nanomechanical sensors to single out active small ligands for ¦Â₂-microglobulin

详细信息    查看全文

• 作者：Giulio Oliviero^a ; ^{giulio.oliviero@ing.unibs.it}Author Vitae ; Marcella Chiari^b ; ^{marcella.chiari@icrm.cnr.it}Author Vitae ; Ersilia De Lorenzi^c ; ^{ersidelo@unipv.it}Author Vitae ; Raffaella Colombo^c ; ^{raffaella.colombo@unipv.it}Author Vitae ; Marina Cretich^b ; ^{marina.cretich@icrm.cnr.it}Author Vitae ; Francesco Damin^b ; ^{francesco.damin@icrm.cnr.it}Author Vitae ; Stefania Federici^a ; ^{stefania.federici@ing.unibs.it}Author Vitae ; Laura E. Depero^a ; ^{laura.depero@ing.unibs.it}Author Vitae ; Paolo Bergese^a ; ^{paolo.bergese@ing.unibs.it}Author Vitae
• 关键词：Small ligands ; ¦Â2-microglobulin ; Conformational changes ; Fibrillogenesis ; Nanomechanics ; Microcantilevers
• 刊名：Sensors and Actuators B: Chemical
• 出版年：2013
• 出版时间：January, 2013
• 年：2013
• 卷：176
• 期：Complete
• 页码：1026-1031
• 全文大小：755 K

文摘

A nanomechanical biosensor based on microcantilevers was implemented to test low molecular weight (small) compounds for their ability to stabilize ¦Â₂-microglobulin (¦Â₂-m) in its native conformation. ¦Â₂-m was immobilized on the top face of silicon microcantilevers and it was demonstrated that pH induced unfolding of the immobilized ¦Â₂-m drives a specific microcantilever bending. This ¦Â₂-m microcantilever assay was then implemented to probe the effect of a pilot set small ligands on ¦Â₂-m conformational stability. Among the tested ligands, congo red was the only one able to protect ¦Â₂-m from unfolding, that is known to be the primary trigger of its self-polymerization into fibrils and in turn of the onset of amyloidosis. These findings disclose the high potentiality of nanomechanical sensors in the field of protein conformation related diseases, as they bring the unique advantage of directly screening compounds for their specific pharmacological activity rather than for generic binding preferences, effectively shortcutting the identification of the active ones.