Effect of Protein Loading Density on the Structure and Biopreservation Efficacy of Metal-Organic Frameworks

Article Effect of Protein Loading Density on the Structure and Biopreservation Efficacy of Metal-Organic Frameworks Yixuan Wang 1,2, Sirimuvva Tadepalli 3,†, Harsh Baldi 1,2, Jeremiah J. Morrissey 1,4 and Srikanth Singamaneni 1,2,4,* 1 Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, St. Louis, MO 63130, USA 2 Institute of Materials Science and Engineering, Washington University in St. Louis, St. Louis, MO 63130, USA 3 Radiation Oncology-Radiation Physics, Stanford School of Medicine, Stanford, CA 94305, USA 4 Siteman Cancer Center, Barnes-Jewish Hospital, and Washington University School of Medicine in St. Louis, St. Louis, MO 63130, USA * Correspondence: [email protected] † Present Affiliation: Department of Immunology, School of Medicine, Stanford University, Stanford, CA 94305, USA Received: 9 September 2024; Revised: 31 October 2024; Accepted: 5 November 2024; Published: 20 November 2024 Abstract: Metal-organic frameworks (MOFs) have emerged as attractive bioencapsulants for preserving the structure and function of various biomolecules against harsh environmental conditions. However, the effect of the loading density of the biomolecules on the structure, physical properties, and biopreservation efficacy of MOF crystals remains elusive. We investigated the structure and properties of zeolitic imidazolate framework (ZIF)-90 crystals as a function of the loading density of a model protein, bovine/human serum albumin (BSA/HSA). We show that the total protein concentration in the MOF growth reaction solution significantly affects the morphology, degree of crystallinity, and biopreservation efficacy of the MOF crystals. The structure integrity and immunologic functionality of albumin remained well-preserved within an optimal protein concentration range of 0.1–1 mg/mL. The proposed optimal range of biomolecule concentration during in situ MOF growth is critical for guiding future research and design endeavors within the rapidly evolving field of MOF-biomedical applications, offering exciting possibilities for biopreservation, drug delivery, and diagnostics.