Login / Signup

Distribution of Ionizable Groups in Polyampholyte Microgels Controls Interactions with Captured Proteins: From Blockade and "Levitation" to Accelerated Release.

Wenjing XuAndrey A RudovRicarda SchroederIvan V PortnovWalter RichteringIgor I PotemkinAndrij Pich
Published in: Biomacromolecules (2019)
A striking discovery in our work is that the distribution of ionizable groups in polyampholyte microgels (random and core-shell) controls the interactions with the captured proteins. Polyampholyte microgels are capable to switch reversibly their charges from positive to negative depending on pH. In this work, we synthesized differently structured polyampholyte microgels with controlled amounts and different distribution of acidic and basic moieties as colloidal carriers to study the loading and release of the model protein cytochrome c (cyt-c). Polyampholyte microgels were first loaded with cyt-c using the electrostatic attraction under pH 8 when the microgels were oppositely charged with respect to the protein. Then the protein release was investigated under different pH (3, 6, and 8) both with experimental methods and molecular dynamics simulations. For microgels with a random distribution of ionizable groups complete and accelerated (compared to polyelectrolyte counterpart) release of cyt-c was observed due to electrostatic repulsive interactions. For core-shell structured microgels with defined ionizable groups, it was possible to entrap the protein inside the neutral core through the formation of a positively charged shell, which acts as an electrostatic potential barrier. We postulate that this discovery allows the design of functional colloidal carriers with programmed release kinetics for applications in drug delivery, catalysis, and biomaterials.
Keyphrases
  • molecular dynamics simulations
  • drug delivery
  • protein protein
  • small molecule
  • amino acid
  • molecular docking
  • cancer therapy
  • high throughput
  • climate change
  • single cell
  • oxide nanoparticles