Tuning Molecular Motion Enhances Intrinsic Fluorescence in Peptide Amphiphile Nanofibers.

Peptide amphiphiles (PAs) are highly tunable molecules that were recently found to exhibit aggregation-induced emission (AIE) when they self-assemble into nanofibers. Here, we leverage decades of molecular design and self-assembly study of PAs to strategically tune their molecular motion within nanofibers to enhance AIE, making them a highly useful platform for applications such as sensing, bioimaging, or materials property characterization. Since AIE increases when aggregated molecules are rigidly and closely packed, we altered the four most closely packed amino acids nearest to the hydrophobic core by varying the order and composition of glycine, alanine, and valine pairs. Of the six PA designs studied, C16VVAAK2 had the highest quantum yield at 0.17, which is a more than 10-fold increase from other PA designs including the very similar C16AAVVK2, highlighting the importance of precise amino acid placement to anchor rigidity closest to the core. We also altered temperature to increase AIE. C16VVAAK2 exhibited an additional 4-fold increase in maximum fluorescence intensity when the temperature was raised from 5 to 65 °C. As the temperature increased, the secondary structure transitioned from ß-sheet to random coil, indicating that further packing an already aligned molecular system makes it even more readily able to transfer energy between the electron-rich amides. This work both unveils a highly fluorescent AIE PA system design and sheds insights into the molecular orientation and packing design traits that can significantly enhance AIE in self-assembling systems.

Synthetic and Computational Design Insights toward Mimicking Protein Binding of Phosphate.

The unique and precise capabilities of proteins are renowned for their specificity and range of application. Effective mimicking of protein-binding offers enticing potential to direct their abilities toward useful applications, but it is nevertheless quite difficult to realize this characteristic of protein behavior in a synthetic material. Here, we design, synthesize, and evaluate experimentally and computationally a series of multicomponent phosphate-binding peptide amphiphile micelles to derive design insights into how protein binding behavior translates to synthetic materials. By inserting the Walker A P-loop binding motif into this peptide synthetic material, we successfully implemented the protein-binding design parameters of hydrogen-bonding and electrostatic interaction to bind phosphate completely and selectively in this highly tunable synthetic platform. Moreover, in this densely arrayed peptide environment, we use molecular dynamics simulations to identify an intriguing mechanistic shift of binding that is inaccessible in traditional proteins, introducing two corresponding new design elements─flexibility and minimization of the loss of entropy due to ion binding, in protein-analogous synthetic materials. We then translate these new design factors to de novo peptide sequences that bind phosphate independent of protein-extracted sequence or conformation. Overall, this work reveals that traditional complex conformational restrictions of binding by proteins can be replaced and repurposed in a multicomponent peptide amphiphile synthetic material, opening up opportunities for future enhanced protein-inspired design.

Intrinsic Fluorescence in Peptide Amphiphile Micelles with Protein-Inspired Phosphate Sensing.

Although peptide amphiphile micelles (PAMs) have been widely studied since they were developed in the late 1990s, to the author's knowledge, there have been no reports that PAMs intrinsically fluoresce without a fluorescent tag, according to the aggregation-induced emission (AIE) effect. This unexpected fluorescence behavior adds noteworthy value to both the peptide amphiphile and AIE communities. For PAMs, intrinsic fluorescence becomes another highly useful feature to add to this well-studied material platform that features precise synthetic control, tunable self-assembly, and straightforward functionalization, with clear potential applications in bioinspired materials for bioimaging and fluorescent sensing. For AIE, it is extremely rare and highly desirable for one platform to exhibit precise tunability on multiple length scales in aqeuous solutions, positioning PAMs as uniquely well-suited for systematic AIE mechanistic study and sequence-specific functionalization for bioinspired AIE applications. In this work, the author proposes that AIE occurs across intermolecular emissive pathways created by the closely packed peptide amide bonds in the micelle corona upon self-assembly, with maximum excitation and emission wavelengths of 355 and 430 nm, respectively. Of the three PAMs evaluated here, the PAM with tightly packed random coil peptide conformation and maximum peptide length had the largest quantum yield, indicating that tuning molecular design can further optimize the intrinsic emissive properties of PAMs. To probe the sensing capabilities of AIE PAMs, a PAM was designed to incorporate a protein-derived phosphate-binding sequence. It detected phosphate down to 1 ppm through AIE-enhanced second-order aggregation, demonstrating that AIE in PAMs leverages tunable biomimicry to perform protein-inspired sensing.

Harnessing Peptide Binding to Capture and Reclaim Phosphate.

With rising consumer demands, society is tapping into wastewater as an innovative source to recycle depleting resources. Novel reclamation technologies have been recently explored for this purpose, including several that optimize natural biological processes for targeted reclamation. However, this emerging field has a noticeable dearth of synthetic material technologies that are programmed to capture, release, and recycle specified targets; and of the novel materials that do exist, synthetic platforms incorporating biologically inspired mechanisms are rare. We present here a prototype of a materials platform utilizing peptide amphiphiles that has been molecularly engineered to sequester, release, and reclaim phosphate through a stimuli-responsive pH trigger, exploiting a protein-inspired binding mechanism that is incorporated directly into the self-assembled material network. This material is able to harvest and controllably release phosphate for multiple cycles of reuse, and it is selective over nitrate and nitrite. We have determined by simulations that the binding conformation of the peptide becomes constrained in the dense micelle corona at high pH such that phosphate is expelled when it otherwise would be preferentially bound. However, at neutral pH, this dense structure conversely employs multichain binding to further stabilize phosphate when it would otherwise be unbound, opening opportunities for higher-order conformational binding design to be engineered into this controllably packed corona. With this work, we are pioneering a new platform to be readily altered to capture other valuable targets, presenting a new class of capture and release materials for recycling resources on the nanoscale.

State Licensing Regulations on Screen Time in Childcare Centers: An Impetus for Participatory Action Research.

BACKGROUND: New licensing regulations require Louisiana early care and education centers (ECEs) to limit children's screen time and increase physical activity. A community- academic partnership involving academic, community, government, and ECE stakeholders launched two initiatives: (1) an evaluation of the implementation of licensing regulations at the local level and (2) a statewide effort to develop technical assistance for ECE directors. OBJECTIVES: To describe the methods and lessons learned and to establish recommendations based on this ongoing participatory action research. METHODS: A case study approach was used to identify the lessons learned and recommendations thus far, based on partners' perspectives and ECE directors' participation. LESSONS LEARNED: Recommendations include to share power and funding among stakeholders, to engage directors as partners to overcome recruitment challenges, and to start with the end in mind to ensure meaningful community engagement. CONCLUSIONS: This participatory action approach is leading to innovative, feasible strategies to increase children's physical activity.