Potassium Ion Mediated Double‐Layered Upright Assembly of Negatively Charged Amyloid‐Like Peptides at Mica/Water Interface

Abstract

Amyloid fibrils were first investigated due to their close association with neurodegenerative diseases, including Alzheimer's, Parkinson's, and Huntington's diseases, [2] wherein soluble peptides/ proteins self-assemble into highly ordered fibrillar structures. [3] Interestingly, subsequent studies have found that amyloid fibrils also play important functional roles in various organisms, including bacteria, [4] insects, [5] and mammals. [6] Moreover, amyloid peptides can self-assemble into highly ordered nanostructures with favorable properties, such as high thermal stability and stiffness as well as biocompatibility. [7] These peptide nanostructures show great promise in tissue engineering, [8] retroviral gene transfer, [9] nanowires, [10] light harvesting, [11] and catalysis. [12] Therefore, new insights into the self-assembly of amyloid-like peptides not only help reveal the pathogenesis of various neurodegenerative diseases but also facilitate the de novo design and fabrication of biomoleculebased nanodevices. Previous studies have suggested that the lipid membrane surface influences the assembly kinetics and morphology of amyloid peptide aggregates. [13] However, cellular membranes and associated physiological conditions are generally too heterogeneous and complex for a clean study of surface-assisted Insight into the surface-assisted self-assembly of amyloid-like peptides is essential to the design and fabrication of novel functional nanomaterials as well as to uncovering the pathogenesis of various neurodegenerative diseases. Despite extensive research, how to control the self-assembly of amyloid-like peptides effectively remains challenging. Here, through a combined experimental and theoretical approach, it is demonstrated that cations could modulate the mica/water interface and further induce the self-assembly of the negatively charged amyloid-like peptide Ac-VGGAVVAGV-COO − (Ac-GAV-9) into multilayered nanofilaments with a surprising all-upright parallel β-sheet conformation. In particular, highly ordered double-layered nanofilaments are observed on the negatively charged mica surfaces in the presence of 0.5-1.5 m KCl. The molecular dynamics simulations further reveal that the double-layered nanofilaments have intriguing parallel β-sheet structures with the C-termini of the first parallel monolayer pointing to the mica surface and the C-termini of the second parallel monolayer pointing to the solvent. Moreover, the stability of the nanofilaments could be modulated by peptide and ion concentrations. Further studies show that the growth of double-layered fibrils at the mica/water interface is a common phenomenon for Ac-GAV-9 in the presence of a variety of salt types.

Direct Visualization of the Dynamic Process of Epsilon Toxin on Hemolysis

“…[32,34] Some amino acids with a strong attraction to the substrate cavity account for their ability to remain stable on the mica. [35,36] According to molecular simulation, the "shoulder by shoulder" arrangement between the C-terminal domains is ensured by the amino acid residues such as lys267 and lys93, and the 𝛽-hairpin domain (amino acid residues 95-175) is oriented away from the up-side, causing the ETX hairpin domain to point outward, exposing the hydrophilic side of the pore arc and encouraging prepore formation. [37] In addition, the amount of specific adsorption sites determines the posture after pre-pores form.…”

Gel-to-Solution Transition of Sulfhydryl Self-Assembled Peptide Hydrogels Undergoing Oxidative Modulation

“…Silicon cantilevers with a nominal spring constant of 48 N m –1 (XSC11, MikroMasch) were used. Before AFM imaging, a drop of 10 μL of the sample was placed on a freshly cleaved mica substrate and allowed to absorb for 5 min, then washed with water, followed by air drying. , …”

“…Before AFM imaging, a drop of 10 μL of the sample was placed on a freshly cleaved mica substrate and allowed to absorb for 5 min, then washed with water, followed by air drying. 20,21 Cell Viability Testing. A cell viability assay kit (Abcam, ab115347) was used to image the live and dead cells.…”