Receptor-ligand rebinding kinetics in confinement

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buir.contributor.authorErbaş, Aykut
dc.citation.epage1624en_US
dc.citation.issueNumber9en_US
dc.citation.spage1609en_US
dc.citation.volumeNumber116en_US
dc.contributor.authorErbaş, Aykuten_US
dc.contributor.authorDe la Cruz, M. O.en_US
dc.contributor.authorMarko, F.en_US
dc.date.accessioned2020-02-07T09:48:34Z
dc.date.available2020-02-07T09:48:34Z
dc.date.issued2019
dc.departmentInstitute of Materials Science and Nanotechnology (UNAM)en_US
dc.departmentNanotechnology Research Center (NANOTAM)en_US
dc.description.abstractRebinding kinetics of molecular ligands plays a key role in the operation of biomachinery, from regulatory networks to protein transcription, and is also a key factor in design of drugs and high-precision biosensors. In this study, we investigate initial release and rebinding of ligands to their binding sites grafted on a planar surface, a situation commonly observed in single-molecule experiments and that occurs in vivo, e.g., during exocytosis. Via scaling arguments and molecular dynamic simulations, we analyze the dependence of nonequilibrium rebinding kinetics on two intrinsic length scales: the average separation distance between the binding sites and the total diffusible volume (i.e., height of the experimental reservoir in which diffusion takes place or average distance between receptor-bearing surfaces). We obtain time-dependent scaling laws for on rates and for the cumulative number of rebinding events. For diffusion-limited binding, the (rebinding) on rate decreases with time via multiple power-law regimes before the terminal steady-state (constant on-rate) regime. At intermediate times, when particle density has not yet become uniform throughout the diffusible volume, the cumulative number of rebindings exhibits a novel, to our knowledge, plateau behavior because of the three-dimensional escape process of ligands from binding sites. The duration of the plateau regime depends on the average separation distance between binding sites. After the three-dimensional diffusive escape process, a one-dimensional diffusive regime describes on rates. In the reaction-limited scenario, ligands with higher affinity to their binding sites (e.g., longer residence times) delay entry to the power-law regimes. Our results will be useful for extracting hidden timescales in experiments such as kinetic rate measurements for ligand-receptor interactions in microchannels, as well as for cell signaling via diffusing molecules.en_US
dc.description.provenanceSubmitted by Zeynep Aykut (zeynepay@bilkent.edu.tr) on 2020-02-07T09:48:34Z No. of bitstreams: 1 Receptor_ligand_rebinding_kinetics_in_confinement.pdf: 2037349 bytes, checksum: ac912abadda3fc0c097ddbef646fca28 (MD5)en
dc.description.provenanceMade available in DSpace on 2020-02-07T09:48:34Z (GMT). No. of bitstreams: 1 Receptor_ligand_rebinding_kinetics_in_confinement.pdf: 2037349 bytes, checksum: ac912abadda3fc0c097ddbef646fca28 (MD5) Previous issue date: 2019en
dc.identifier.doi10.1016/j.bpj.2019.02.033en_US
dc.identifier.issn0006-3495
dc.identifier.urihttp://hdl.handle.net/11693/53160
dc.language.isoEnglishen_US
dc.publisherBiophysical Societyen_US
dc.relation.isversionofhttps://dx.doi.org/10.1016/j.bpj.2019.02.033en_US
dc.source.titleBiophysical Journalen_US
dc.subjectMolecular ligandsen_US
dc.subjectRebinding kineticsen_US
dc.subjectLigand-receptor interactionsen_US
dc.subjectReceptor-ligand rebinding kineticsen_US
dc.titleReceptor-ligand rebinding kinetics in confinementen_US
dc.typeArticleen_US

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