title: Site-Specific Modulation of Charge Controls the Structure and Stimulus Responsiveness of Intrinsically Disordered Peptide Brushes.
abstract: Intrinsically disordered proteins (IDPs) are an important and emerging class of materials for tailoring biointerfaces. While the importance of chain charge and resultant electrostatic interactions in controlling conformational properties of IDPs is beginning to be explored through in silico approaches, there is a dearth of experimental studies motivated toward a systematic study of these effects. In an effort to explore this relationship, we measured the conformations of two peptides derived from the intrinsically disordered neurofilament (NF) side arm domain: one depicting the wild-type sequence with four lysine-serine-proline repeats (KSP peptide) and another in which the serine residues were replaced with aspartates (KDP peptide), a strategy sometimes used to mimic phosphorylation. Using a variety of biophysical measurements including a novel application of scanning angle interference microscopy, we demonstrate that the KDP peptide assumes comparatively more expanded conformations in solution and forms significantly thicker brushes when immobilized on planar surfaces at high densities. In both settings, the peptides respond to changes in ambient ionic strength, with each peptide showing distinct stimulus-responsive characteristics. While the KDP peptide undergoes compaction with increasing ionic strength as would be expected for a polyampholyte, the KSP peptide shows biphasic behavior, with an initial compaction followed by an expanded state at a higher ionic strength. Together these results support the notion that modulation of charge on IDPs can regulate conformational and interfacial properties.
authors.affiliation: Department of Bioengineering, University of California, Berkeley , Berkeley, California 94720, United States.
authors.forename: Maniraj
authors.initials: M
authors.lastname: Bhagawati
authors.affiliation: Center for Bioengineering and Tissue Regeneration, University of California, San Francisco , San Francisco, California 94143, United States.|UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, Berkeley , Berkeley, California 94720, United States.
authors.forename: Matt G
authors.initials: MG
authors.lastname: Rubashkin
authors.affiliation: Department of Bioengineering, University of California, Berkeley , Berkeley, California 94720, United States.|Department of Chemistry, University of California, Berkeley , Berkeley, California 94720, United States.
authors.forename: Jessica P
authors.initials: JP
authors.lastname: Lee
authors.affiliation: Department of Bioengineering, University of California, Berkeley , Berkeley, California 94720, United States.
authors.forename: Badriprasad
authors.initials: B
authors.lastname: Ananthanarayanan
authors.affiliation: Center for Bioengineering and Tissue Regeneration, University of California, San Francisco , San Francisco, California 94143, United States.|UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, Berkeley , Berkeley, California 94720, United States.
authors.forename: Valerie M
authors.initials: VM
authors.lastname: Weaver
authors.affiliation: Department of Bioengineering, University of California, Berkeley , Berkeley, California 94720, United States.|UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, Berkeley , Berkeley, California 94720, United States.|Department of Chemical and Biomolecular Engineering, University of California, Berkeley , Berkeley, California 94720, United States.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kumar
mesh_terms: D064267:Intrinsically Disordered Proteins / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary
chemical_list: D064267:Intrinsically Disordered Proteins; D010455:Peptides