Collaborative Research: Magnetically Assisted Self-Assembly for Facile 2D Membrane Protein Crystallization

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Non-Technical Membrane proteins are cells' primary mechanism for interacting with the external environment, and thus demonstrate exceptionally fine-tuned capabilities in sensing, selective transport, and catalysis. This award to study Magnetically Assisted Self-Assembly for Facile 2D Membrane Protein Crystallization will support fundamental research on the magnetic properties of these membrane proteins, and biological materials more generally. The PIs will leverage their knowledge of membrane protein behavior in magnetic fields to support the development of two-dimensional crystals from these biological materials. Finally, these crystals will be deployed in devices for highly selective sensing and separation applications. In parallel, the project will fund the expansion of an undergraduate research training and mentorship program that includes a formal 3-hour training process for PhD student supervisors of undergraduate students, a formal goal-setting process for incoming undergraduate researchers, and a 360-degree evaluation process for undergraduates, PhD supervisors, and the PI conducted on a bi-monthly basis and upon completion of the project. Technical PIs propose to investigate the fundamental physics and chemistry of membrane protein (MP) self-assembly in the presence of a magnetic field to inform strategies for scalable 2D crystallization of MPs with high crystalline order realized over large areas. They will compute the diamagnetic susceptibility of MPs and supporting matrices (block co-polymers and lipids) to assess the generalizability of this technique across known MPs and to inform subsequent self-assembly simulations. A novel coarse-grain model will be developed to describe the self-assembly of MP crystals in the presence and absence of an applied magnetic field. This model will be sufficiently efficient as to serve as a front-end biomaterial fabrication design tool across diverse combinations of MPs and supporting matrices. PIs will validate these models by experimentally characterizing the effect of magnetic fields on MP crystallization under diverse experimental conditions. Finally, 2D MP crystals of OmpF and pHR will be tested as model systems for screening ligands and blockers in comparison with current state-of-the-art bilayer type systems. This work will contribute 1) a novel approach for computing the diamagnetic anisotropy and diamagnetic susceptibility of large molecules in which primary, secondary, and tertiary structure each contribute to the magnetic properties of the molecule, 2) a physical understanding of the various competing forces that drive the kinetics and final state of self-assembly, 3) a modeling tool to guide experimental design for the fabrication of 2D MP crystals, and 4) a demonstration of 2D MP crystals in functional devices and an assessment of their performance relative to the current state-of-the-art.