Rationally Tailored Mesoporous Hosts for Optimal Protein Encapsulation

Proteins play important roles in the therapeutic, medicaldiagnostic,and chemical catalysis industries. However, their potential is oftenlimited by their fragile and dynamic nature outside cellular environments.The encapsulation of proteins in solid materials has been widely pursuedas a route to enhance their stability and ease of handling. Nevertheless,the experimental investigation of protein interactions with rationallydesigned synthetic hosts still represents an area in need of improvement.In this work, we leveraged the tunability and crystallinity of metal-organicframeworks (MOFs) and developed a series of crystallographically definedprotein hosts with varying chemical properties. Through systematicstudies, we identified the dominating mechanisms for protein encapsulationand developed a host material with well-tailored properties to effectivelyencapsulate the protein ubiquitin. Specifically, in our mesoporoushosts, we found that ubiquitin encapsulation is thermodynamicallyfavored. A more hydrophilic encapsulation environment with favorableelectrostatic interactions induces enthalpically favored ubiquitin-MOFinteractions, and a higher pH condition reduces the intraparticlediffusion barrier, both leading to a higher protein loading. Our findingsprovide a fundamental understanding of host-guest interactionsbetween proteins and solid matrices and offer new insights to guidethe design of future protein host materials to achieve optimal proteinloading. The MOF modification technique used in this work also demonstratesa facile method to develop materials easily customizable for encapsulatingproteins with different surface properties.

Automated summary

Proteins play important roles in various industries, but their fragility outside of cells limits their potential. Encapsulating proteins in solid materials can enhance their stability, but there is still room for improvement in understanding their interactions with synthetic hosts.