Mohanram, H. | Search bioRxiv

bioRxiv2023

Harnessing Gradients for Self-Assembly of Peptide-Based Nanocapsules: A Pathway to Advanced Drug Delivery Systems

Biological systems often create materials with intricate structures to achieve specialized functions. In comparison, precise control of structures in man-made materials has been challenging. Here, we report a serendipitous discovery of insect cuticle peptides (ICPs) spontaneously forming nanocapsules through a single-step solvent exchange process, where the concentration gradient resulting from mixing of water and aceton drives the localization and self-assembly of the peptides into hollow nanocapsules. The underlying driving force is the intrinsic affinity of the peptides for a particular solvent concentration, while the diffusion of water and acetone creates a gradient interface that triggers peptide localization and self-assembly. This gradient-mediated self-assembly offers a transformative pathway towards next-generation drug delivery systems based on peptide nanocapsules.

bioengineering↗

bioRxiv2020

Structure of a consensus chitin-binding domain revealed by solution NMR

Carbohydrate-binding proteins (CBPs) are a versatile group of proteins found in almost every organism on earth. CBPs are involved in enzymatic carbohydrate degradation and also serve as templating scaffolds in the exoskeleton of crustaceans and insects. One specific chitin-binding motif found across a wide range of arthropods exoskeletons is the "extended Rebers and Riddiford" consensus (R&R). However, how the R&R motif binds chitin is unclear. Here, we report the 3D structure and molecular level interactions of a chitin-binding domain (CBD-{gamma}) located in a CBP from the beak of the jumbo squid Dosidicus gigas. This CBP is one of four chitin-binding proteins identified in the beak mouthpart of D. gigas and is believed to interact with chitin to form a scaffold network that is infiltrated with a second set of structural proteins during beak maturation. We used solution state NMR spectroscopy to elucidate the molecular interactions between CBD-{gamma} and the soluble chitin derivative pentaacetyl-chitopentaose (PCP) and find that folding of this domain is triggered upon its interaction with PCP. To our knowledge, this is the first experimental 3D structure of a CBP containing the R&R consensus motif, which can be used as a template to understand in more details the role of the R&R motif found in a wide range of CBP-chitin complexes. The present structure also provides molecular information for biomimetic synthesis of graded biomaterials using aqueous-based chemistry and biopolymers.

biochemistry↗