Leveraging Isothermal Titration Calorimetry to Explore Structure–Property Relationships of Protein Immobilization in Metal–Organic Frameworks

Abstract

Proteins immobilized in metal–organic frameworks (MOFs) often show extraordinary stability. However, most efforts to immobilize proteins in MOFs have only been exploratory. Herein, we present the first systematic study on the thermodynamics of protein immobilization in MOFs. Using insulin as a probe, we leveraged isothermal titration calorimetry (ITC) to investigate how topology, pore size, and hydrophobicity of MOFs influence immobilization. ITC data obtained from the encapsulation of insulin in a series of Zr‐MOFs reveals that MOFs provide proteins with a hydrophobic stabilizing microenvironment, making the encapsulation entropically driven. In particular, the pyrene‐based NU‐1000 tightly encapsulates insulin in its ideally sized mesopores and stabilizes insulin through π‐π stacking interactions, resulting in the most enthalpically favored encapsulation process among this series. This study reveals critical insights into the structure–property relationships of protein immobilization.

Document Details

Document Type
Pub Defense Publication
Publication Date
Aug 09, 2022
Source ID
10.1002/anie.202209110

Entities

People

  • Fanrui Sha
  • Kaikai Ma
  • Kent O Kirlikovali
  • Omar Farha
  • Satoshi Kato
  • Shengyi Su
  • Timur Islamoglu
  • Tzu‐Yi Tai
  • Xiaoliang Wang
  • Xingjie Wang

Organizations

  • Defense Threat Reduction Agency
  • National Science Foundation
  • National Science and Technology Council
  • Northwestern University
  • United States Army

Tags

Readers

  • Agricultural Chemistry/Soil Science
  • Molecular and Cellular Biology
  • Systems Analysis and Design