title: Two Complementary Approaches for the Controlled Release of Biomolecules Immobilized via Coiled-Coil Interactions: Peptide Core Mutations and Multivalent Presentation.
abstract: We have developed a heterodimeric coiled-coil system based on two complementary peptides, namely (EVSALEK)5and (KVSALKE)5, or E and K, for the attachment of E-tagged biomolecules onto K-decorated biomaterials. We here explore two approaches to control the strength and the stability of the E/K coiled-coil complex, and thus its potential for the controlled release of biomolecules. Those are Leucine-to-Alanine mutations in the K peptide (4 peptides with 0 to 3 mutations) and multivalent presentation of the E peptide (6 bio-objects from monomeric to dimeric and n-meric). Using E-tagged growth factors and nanoparticles as models, SPR-based assays performed under continuous flow indicated that the release rate was strongly affected by both approaches independently, and that the strength of the capture could be finely tuned over a wide range (apparent dissociation constant from 0.12 pM to 270 nM). Further release assays carried out in well-plates showed that the multivalent presentation only had a significant influence in this setup since the wells were not rinsed under continuous flow.
authors.affiliation: Department of Chemical Engineering, Groupe de Recherche en Sciences et Technologies Biomédicales (GRSTB), Bio-P2 Research Unit, École Polytechnique de Montréal , P.O. Box 6079, succursale Centre-Ville, Montréal, Quebec H3C 3A7, Canada.
authors.forename: Frederic
authors.initials: F
authors.lastname: Murschel
authors.affiliation: Department of Chemical Engineering, Groupe de Recherche en Sciences et Technologies Biomédicales (GRSTB), Bio-P2 Research Unit, École Polytechnique de Montréal , P.O. Box 6079, succursale Centre-Ville, Montréal, Quebec H3C 3A7, Canada.
authors.forename: Charles
authors.initials: C
authors.lastname: Fortier
authors.affiliation: Department of Chemical Engineering, Groupe de Recherche en Sciences et Technologies Biomédicales (GRSTB), Bio-P2 Research Unit, École Polytechnique de Montréal , P.O. Box 6079, succursale Centre-Ville, Montréal, Quebec H3C 3A7, Canada.
authors.forename: Mario
authors.initials: M
authors.lastname: Jolicoeur
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado, School of Medicine , Anschutz Medical Campus, Aurora, Colorado 80045, United States.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Hodges
authors.affiliation: Department of Chemical Engineering, Groupe de Recherche en Sciences et Technologies Biomédicales (GRSTB), Bio-P2 Research Unit, École Polytechnique de Montréal , P.O. Box 6079, succursale Centre-Ville, Montréal, Quebec H3C 3A7, Canada.
authors.forename: Gregory
authors.initials: G
authors.lastname: De Crescenzo
mesh_terms: D000595:Amino Acid Sequence; D001672:Biocompatible Materials / Q000737:chemistry*; D002942:Circular Dichroism; D003692:Delayed-Action Preparations / Q000737:chemistry*; D019281:Dimerization; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D053758:Nanoparticles / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D010455:Peptides