Single Amino Acid Modifications for Controlling the Helicity of Peptide-Based Chiral Gold Nanoparticle Superstructures.

Assembling nanoparticles (NPs) into well-defined superstructures can lead to emergent collective properties that depend on their 3-D structural arrangement. Peptide conjugate molecules designed to both bind to NP surfaces and direct NP assembly have proven useful for constructing NP superstructures, and atomic- and molecular-level alterations to these conjugates have been shown to manifest in observable changes to nanoscale structure and properties. The divalent peptide conjugate, C16-(PEPAu)2 (PEPAu = AYSSGAPPMPPF), directs the formation of one-dimensional helical Au NP superstructures. This study examines how variation of the ninth amino acid residue (M), which is known to be a key Au anchoring residue, affects the structure of the helical assemblies. A series of conjugates of differential Au binding affinities based on variation of the ninth residue were designed, and Replica Exchange with Solute Tempering (REST) Molecular Dynamics simulations of the peptides on an Au(111) surface were performed to determine the approximate surface contact and to assign a binding score for each new peptide. A helical structure transition from double helices to single helices is observed as the peptide binding affinity to the Au(111) surface decreases. Accompanying this distinct structural transition is the emergence of a plasmonic chiroptical signal. REST-MD simulations were also used to predict new peptide conjugate molecules that would preferentially direct the formation of single-helical AuNP superstructures. Significantly, these findings demonstrate how small modifications to peptide precursors can be leveraged to precisely direct inorganic NP structure and assembly at the nano- and microscale, further expanding and enriching the peptide-based molecular toolkit for controlling NP superstructure assembly and properties.

Leveraging Peptide Sequence Modification to Promote Assembly of Chiral Helical Gold Nanoparticle Superstructures.

Peptide conjugate molecules comprising a gold-binding peptide (e.g., AYSSGAPPMPPF) attached to an aliphatic tail have proven to be powerful agents for directing the synthesis and assembly of gold nanoparticle superstructures, in particular chiral helices having interesting plasmonic chiroptical properties. The composition and structure of these molecular agents can be tailored to carefully tune the structure and properties of gold nanoparticle single and double helices. To date, modifications to the ß-sheet region (AYSSGA) of the peptide sequence have not been exploited to control the metrics and assembly of such superstructures. We report here that systematic peptide sequence variation in a series of gold-binding peptide conjugate molecules can be leveraged not only to affect the assembly of peptide conjugates but also to control the synthesis, assembly, and optical properties of gold nanoparticle superstructures. Depending upon the hydrophobicity of a single-amino acid variant, the conjugates yield either dispersed gold nanoparticles or helical superstructures. These results provide evidence that subtle changes to peptide sequence, via single-amino acid variation in the ß-sheet region, can be leveraged to program structural control in chiral gold nanoparticle superstructures.

Molecular Modulator Approach for Controlling the Length of Chiral 1D Single-Helical Gold Nanoparticle Superstructures.

Peptide-based methods have proven useful for constructing helical gold nanoparticle superstructures that exhibit strong plasmonic chiroptical activity. Superstructure syntheses using the amphiphilic peptide conjugate C16-(AYSSGAPPMoxPPF)2 typically yield 1D helices with a broad length distribution. In this study, we introduce a molecular modulator approach for controlling helix length. It represents a first step toward achieving narrowly disperse populations of single helices fabricated using peptide-based methods. Varying amounts of modulator, C16-(AYSSGA)2, were added to C16-(AYSSGAPPMoxPPF)2-based single-helix syntheses, resulting in decreased helix length and narrowing of the helix length distribution. Kinetic studies of fiber assembly were performed to investigate the mechanism by which the modulator affects helix length. It was found that the modulator leads to rapid peptide conjugate nucleation and fiber growth, which in turn results in large amounts of short fibers that serve as the underlying scaffold for the single-helix superstructures. These results constitute important advances toward generating monodisperse samples of plasmonic helical colloids.

Construction of Chiral, Helical Nanoparticle Superstructures: Progress and Prospects.

Chiral nanoparticle (NP) superstructures, in which discrete NPs are assembled into chiral architectures, represent an exciting and growing class of nanomaterials. Their enantiospecific properties make them promising candidates for a variety of potential applications. Helical NP superstructures are a rapidly expanding subclass of chiral nanomaterials in which NPs are arranged in three dimensions about a screw axis. Their intrinsic asymmetry gives rise to a variety of interesting properties, including plasmonic chiroptical activity in the visible spectrum, and they hold immense promise as chiroptical sensors and as components of optical metamaterials. Herein, a concise history of the foundational conceptual advances that helped define the field of chiral nanomaterials is provided, and some of the major achievements in the development of helical nanomaterials are highlighted. Next, the key methodologies employed to construct these materials are discussed, and specific merits that are offered by each assembly methodology are identified, as well as their potential disadvantages. Finally, some specific examples of the emerging applications of these materials are discussed and some areas of future development and research focus are proposed.

The patient perspective: arthritis care provided by Advanced Clinician Practitioner in Arthritis Care program-trained clinicians.

OBJECTIVE: To assess patient satisfaction with the arthritis care services provided by graduates of the Advanced Clinician Practitioner in Arthritis Care (ACPAC) program. MATERIALS AND METHODS: This was a cross-sectional evaluation using a self-report questionnaire for data collection. Participants completed the Patient-Doctor Interaction Scale, modified to capture patient-practitioner interactions. Participants completed selected items from the Group Health Association of America's Consumer Satisfaction Survey, and items capturing quality of care, appropriateness of wait times, and a comparison of extended-role practitioner (ERP) services with previously received arthritis care. RESULTS: A total of 325 patients seen by 27 ERPs from 15 institutions completed the questionnaire. Respondents were primarily adults (85%), female (72%), and living in urban areas (79%). The mean age of participants was 54 years (range 3-92 years), and 51% were not working. Patients with inflammatory (51%) and noninflammatory conditions (31%) were represented. Mean (standard deviation) Patient-Practitioner Interaction Scale subscale scores ranged from 4.50 (0.60) to 4.63 (0.48) (1 to 5 [greater satisfaction]). Overall satisfaction with the quality of care was high (4.39 [0.77]), as was satisfaction with wait times (referral to appointment, 4.27 [0.86]; in clinic, 4.24 [0.91]). Ninety-eight percent of respondents felt the arthritis care they received was comparable to or better than that previously received from other health care professionals. CONCLUSION: Patients were very satisfied with and amenable to arthritis care provided by graduates of the ACPAC program. Our findings provide early support for the deployment and integration of ACPAC ERPs into the Ontario health care system and should inform future evaluation at the patient level.