Direct measurement of the energy landscape of ligand-receptor interactions

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dc.contributor.advisorFlorin, Ernst-Ludwigen
dc.contributor.committeeMemberShubeita, George T.en
dc.creatorSchwemmer, Frank Heinz, 1986-en
dc.date.accessioned2011-01-04T16:31:02Zen
dc.date.accessioned2011-01-04T16:31:13Zen
dc.date.accessioned2017-05-11T22:21:00Z
dc.date.available2011-01-04T16:31:02Zen
dc.date.available2011-01-04T16:31:13Zen
dc.date.available2017-05-11T22:21:00Z
dc.date.issued2010-08en
dc.date.submittedAugust 2010en
dc.date.updated2011-01-04T16:31:13Zen
dc.descriptiontexten
dc.description.abstractIn this thesis, a novel single molecule technique will be presented that will, for the first time, give direct access to the interaction energy landscapes of small molecules. The technique relies on the interpretation of thermal position fluctuations of a colloidal probe particle tethered to the molecular complex of interest and a geometrical amplification effect that converts Ångstrom scale fluctuations of the ligand in the binding pocket of the receptor to tens of nanometer fluctuation of the bead. The position of the bead is measured with 0.5 MHz bandwidth and 2 nm spatial resolution. The surface characteristic of the substrate was found to be critical for this new technique and various surface effects were observed. Methods were developed to block nonspecific interaction between the surfaces. The mobility of specifically bound particles was found to depend strongly on the density of specific bonds and the length of the molecular complex; low concentration and short linker lead to slow ligand-receptor mediated surface diffusion, high concentration and/or long linkers to an immobilization of the particle. Transient bond formation was observed for the intermediate range. Details of the interaction energy landscape were not resolved. However, a systematic change in the linker length from 22 Å to 29 Å led to a corresponding change in the lateral position fluctuations from 12.9 nm to 13.2 nm in excellent agreement with our theoretical calculations, confirming the geometrical amplification effect. Also, a new phenomenon of nanometer scale friction in the gap between the bead and the surface was discovered. In summary, the results underline that the novel technique might be able to measure details of the interaction energy landscape of a specific ligand-receptor bond and thus test theoretical predictions for its shape.en
dc.description.departmentPhysicsen
dc.format.mimetypeapplication/pdfen
dc.identifier.urihttp://hdl.handle.net/2152/ETD-UT-2010-08-1970en
dc.language.isoengen
dc.subjectLiganden
dc.subjectReceptoren
dc.subjectForcesen
dc.subjectSpecific interactionen
dc.subjectSingle moleculeen
dc.subjectBiophysicsen
dc.subjectAvidinen
dc.subjectBiotinen
dc.subjectEnergy landscapeen
dc.titleDirect measurement of the energy landscape of ligand-receptor interactionsen
dc.type.genrethesisen

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