Ordered Conformation-Regulated Vesicular Membrane Permeability

Angew Chem Int Ed Engl. 2021 Oct 4;60(41):22529-22536. doi: 10.1002/anie.202109637. Epub 2021 Sep 9.

Abstract

In nature, the folding and conformation of proteins can control the cell or organelle membrane permeability and regulate the life activities. Here we report the first example of synthetic polypeptide vesicles that regulate their permeability via ordered transition of secondary conformations, in a manner similar to biological systems. The polymersomes undergo a β-sheet to α-helix transition in response to reactive oxygen species (ROS), leading to wall thinning without loss of vesicular integrity. The change of membrane structure increases the vesicular permeability and enables specific transport of payloads with different molecular weights. As a proof-of-concept, the polymersomes encapsulating enzymes could serve as nanoreactors and carries for glucose-stimulated insulin secretion in vivo inspired by human glucokinase, resulting in safe and effective treatment of type 1 diabetes mellitus in mouse models. This study will help understand the biology of biomembranes and facilitate the engineering of nanoplatforms for biomimicry, biosensing, and controlled delivery applications.

Keywords: biomimetic; conformation; permeability; polypeptides; vesicles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Membrane Permeability / drug effects
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Disease Models, Animal
  • Hypoglycemic Agents / chemical synthesis
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology*
  • Mice
  • Molecular Conformation
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Peptides / pharmacology*

Substances

  • Hypoglycemic Agents
  • Peptides