title: Force spectroscopy of multivalent binding of riboflavin-conjugated dendrimers to riboflavin binding protein.
abstract: Putative riboflavin receptors are considered as biomarkers due to their overexpression in breast and prostate cancers. Hence, these receptors can be potentially exploited for use in targeted drug delivery systems where dendrimer nanoparticles with multivalent ligand attachments can lead to greater specificity in cellular interactions. In this study, the single molecule force spectroscopy technique was used to assess the physical strength of multivalent interactions by employing a riboflavin (RF)-conjugated generation 5 PAMAM dendrimer G5(RF)n nanoparticle. By varying the average RF ligand valency (n = 0, 3, 5), the rupture force was measured between G5(RF)n and the riboflavin binding protein (RFBP). The rupture force increased when the valency of RF increased. We observed at the higher valency (n = 5) three binding events that increased in rupture force with increasing loading rate. Assuming a single energy barrier, the Bell-Evans model was used to determine the kinetic off-rate and barrier width for all binding interactions. The analysis of our results appears to indicate that multivalent interactions are resulting in changes to rupture force and kinetic off-rates.
authors: Abigail N
authors: AN
authors: Leistra
authors: Jong Hyun
authors: JH
authors: Han
authors: ‡Michigan Nanotechnology Institute for Medicine and Biological Sciences, Ann Arbor, Michigan 48109, United States.
authors: Shengzhuang
authors: S
authors: Tang
authors: ‡Michigan Nanotechnology Institute for Medicine and Biological Sciences, Ann Arbor, Michigan 48109, United States.|⊥Department of Physics, University of Michigan, Ann Arbor, Michigan 48109, United States.
authors: Bradford G
authors: BG
authors: Orr
authors: ‡Michigan Nanotechnology Institute for Medicine and Biological Sciences, Ann Arbor, Michigan 48109, United States.|§Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, United States.|∥Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109, United States.
authors: Mark M
authors: MM
authors: Banaszak Holl
authors: ‡Michigan Nanotechnology Institute for Medicine and Biological Sciences, Ann Arbor, Michigan 48109, United States.|#Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, United States.
authors: Seok Ki
authors: SK
authors: Choi
authors: Kumar
authors: K
authors: Sinniah
mesh_terms: D002151:Calorimetry; D050091:Dendrimers / Q000737:chemistry*; D007700:Kinetics; D026901:Membrane Transport Proteins / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D053758:Nanoparticles / Q000737:chemistry*; D011485:Protein Binding; D012256:Riboflavin / Q000737:chemistry*; D013057:Spectrum Analysis; D013816:Thermodynamics
chemical_list: D050091:Dendrimers; D026901:Membrane Transport Proteins; C104700:PAMAM Starburst; C019079:riboflavin-binding protein; D012256:Riboflavin