Self-Assembly of an α-Helical Peptide into a Crystalline Two-Dimensional Nanoporous Framework.

Sequence-specific peptides have been demonstrated to self-assemble into structurally defined nanoscale objects including nanofibers, nanotubes, and nanosheets. The latter structures display significant promise for the construction of hybrid materials for functional devices due to their extended planar geometry. Realization of this objective necessitates the ability to control the structural features of the resultant assemblies through the peptide sequence. The design of a amphiphilic peptide, 3FD-IL, is described that comprises two repeats of a canonical 18 amino acid sequence associated with straight α-helical structures. Peptide 3FD-IL displays 3-fold screw symmetry in a helical conformation and self-assembles into nanosheets based on hexagonal packing of helices. Biophysical evidence from TEM, cryo-TEM, SAXS, AFM, and STEM measurements on the 3FD-IL nanosheets support a structural model based on a honeycomb lattice, in which the length of the peptide determines the thickness of the nanosheet and the packing of helices defines the presence of nanoscale channels that permeate the sheet. The honeycomb structure can be rationalized on the basis of geometrical packing frustration in which the channels occupy defect sites that define a periodic superlattice. The resultant 2D materials may have potential as materials for nanoscale transport and controlled release applications.

Two-Dimensional Peptide and Protein Assemblies.

Two-dimensional nanoscale assemblies (nanosheets) represent a promising structural platform to arrange molecular and supramolecular substrates with precision for integration into devices. This nanoarchitectonic approach has gained significant traction over the last decade, as a general concept to guide the fabrication of functional nanoscale devices. Sequence-specific biomolecules, e.g., peptides and proteins, may be considered excellent substrates for the fabrication of two-dimensional nanoarchitectonics. Molecular level instructions can be encoded within the sequence of monomers, which allows for control over supramolecular structure if suitable design principles could be elaborated. Due to the complexity of interactions between protomers, the development of principles aimed toward rational design of peptide and protein nanosheets is at a nascent stage. This review discusses the known two-dimensional peptide and protein assemblies to further our understanding of how to control the arrangement of molecules in two-dimensions.

Controlling self-assembly of a peptide-based material via metal-ion induced registry shift.

Peptide TZ1C2 can populate two distinct orientations: a staggered (out-of-register) fibril and an aligned (in-register) coiled-coil trimer. The coordination of two cadmium ions induces a registry shift that results in a reversible transition between these structural forms. This process recapitulates the self-assembly mechanism of native protein fibrils in which a ligand binding event gates a reversible conformational transition between alternate forms of a folded peptide structure.

A high-throughput chemotaxis detection method for CCR4+ T cell migration inhibition using image cytometry.

Chemotaxis is an important aspect of immune cell behavior within the tumor microenvironment (TME). One prominent example of chemotaxis within the TME is the migration of regulatory T cells (Tregs) in response to the chemokine ligands CCL17 and CCL22. Tregs within the TME cause the suppression of anti-tumor immunity and inhibition of the effect of immunotherapeutic treatments. Therefore, the ability to screen for therapeutic antibodies that can inhibit or stimulate the chemotaxis of various immune cell types is crucial. Traditionally, chemotaxis is studied by determining the number of cells in the bottom reservoir of a Transwell microplate using flow cytometry; however, this method is time-consuming and thus not appropriate for high-throughput screening purposes. The Celigo Image Cytometer has been employed to perform high-throughput cell-based assays and was used to develop a new detection method for chemotaxis measurement. The image-based detection method was developed using chemokine ligands CCL17 and CCL22 to induce the migration of CCR4+ T cells and directly count them on the bottom of the Transwell plates. Finally, the method was applied to measure the inhibitory effects of commercially available anti-CCL17 and anti-CCL22 antibodies, which caused a dose-dependent decrease in the number of migrated T cells. The proposed image cytometry method allowed screening of multiple antibodies at various concentrations, simultaneously, which can improve the efficiency for discovering potential antibody candidates that can induce or inhibit recruitment of immune cells to the tumor microenvironment.

The latest animal models of ovarian cancer for novel drug discovery.

INTRODUCTION: Epithelial ovarian cancer is a heterogeneous disease classified into five subtypes, each with a different molecular profile. Most cases of ovarian cancer are diagnosed after metastasis of the primary tumor and are resistant to traditional platinum-based chemotherapeutics. Mouse models of ovarian cancer have been utilized to discern ovarian cancer tumorigenesis and the tumor's response to therapeutics. Areas covered: The authors provide a review of mouse models currently employed to understand ovarian cancer. This article focuses on advances in the development of orthotopic and patient-derived tumor xenograft (PDX) mouse models of ovarian cancer and discusses current humanized mouse models of ovarian cancer. Expert opinion: The authors suggest that humanized mouse models of ovarian cancer will provide new insight into the role of the human immune system in combating and augmenting ovarian cancer and aid in the development of novel therapeutics. Development of humanized mouse models will take advantage of the NSG and NSG-SGM3 strains of mice as well as new strains that are actively being derived.

Geometrical frustration as a potential design principle for peptide-based assemblies.

Two-dimensional peptide and protein assemblies have been the focus of increased scientific research as they display significant potential for the creation of functional nanomaterials. Soluble subunits derived from a variety of protein motifs have been demonstrated to self-assemble into structurally defined nanosheets under environmentally benign conditions in which the components often retain their native structure and function. These types of two-dimensional assemblies may have an advantage for nanofabrication in that their extended planar shapes can be more straightforwardly incorporated into the current formats of nanoscale devices. However, significant challenges remain in the fabrication of these materials, particularly in devising methods to control the size, shape and internal structure of the resultant materials. Geometrical frustration may be envisioned as a possible mechanism to exert control over these structural parameters through rational design. While this objective has yet to be realized in practice, we discuss in this article the potential role of geometrical frustration as a principle to rationalize unusual self-assembly behaviour in several examples of two-dimensional peptide assemblies.