The Medina group employs a multidisciplinary approach that interfaces chemical biology, supramolecular chemistry and self-assembly to develop materials-enabled strategies for grand challenges in human health. Insights gained from studying peptide, protein and carbohydrate assembly, at both the nano- and micro-scale, are used to design adaptive molecular networks and living matter that can spatiotemporally control cellular functions and augment biologic responses. Ultimately, we seek to invent technologies that can be rapidly translated into the clinic to improve human health. Current and on-going projects in the group include:
Ultrasound-Programmable Biomaterials
Proteins, peptides and nucleic acids are some of the most potent and selective tools in precision medicine. In particular, biomacromolecules which can sense, track and disrupt intracellular pathways represent emerging biosensors and drug candidates, that could open unprecedented diagnostic and therapeutic opportunities, if properly delivered into cells. However, their macromolecular nature often prohibits their delivery across cell membranes to reach their intracellular target. We have recently developed a new class of self-assembled peptide nano-carrier, termed a ‘nano-peptisome’, that can be ruptured via ultrasound to deliver cell-impermeable cargo directly into target cells with high spatial resolution. We are leveraging this technology to study biomolecular interactions of living cells in real-time, as well as developing intracellularly targeted therapies to disrupt dynamic vulnerabilities in diseased cells and perform site-specific gene editing.
Related Publications:
J. N. Sloand, E. Rokni, C. T. Watson, M. A. Miller, K. B. Manning, J. C. Simon, S. H. Medina*. Ultrasound-Responsive Nanopeptisomes Enable Synchronous Spatial Imaging and Inhibition of Clot Growth in Deep Vein Thrombosis. Advanced Healthcare Materials. 2021: 2100520.
A. Lawanprasert, A. Chau, J. N. Sloand, S. Hannifin, S. H. Medina*. Tuning the Interfacial Properties of Fluorous Colloids Towards Ultrasound Programmable Bioactivity. ACS Applied Materials & Interfaces. 2021, 13(5): 5989-5998
J. N. Sloand, T. T. Nguyen, S. A. Zinck, E. C. Cook, T. J. Zimudzi, S. A. Showalter, A. B. Glick, J. C. Simon, S. H. Medina*. Ultrasound-Guided Cytosolic Antibody Delivery via Transient Fluorous Masks. ACS Nano. 2020, https://doi.org/10.1021/acsnano.9b08745.
‘Trojan-Horse’ Microbial Biotechnologies
Bacteria play central roles in human health and disease. Microorganisms that colonizing our body, collectively known as the ‘microbiome’, are central to homeostasis at the cell, organ and system levels. However, overexposure to antibiotics can foster emergence of drug resistance genes which, through horizontal gene transfer, accelerate and promote multidrug-resistant infections. Biomaterials that regulate these microbial communities represent powerful strategies to treat bacterial infections and engineer commensal populations. We are developing biomimetic antimicrobials and bio-inspired peptide-polysaccharide particles that lure, engage and rapidly kill drug-resistant microbes. Our group is also developing bacterial-derived ‘living’ materials designed to interact with commensal flora in the human oral, pulmonary and gastrointesinal tracts to engineer the local microbiome and re-establish tissue homeostasis during diseased states.
Related Publications:
A. W. Simonson, T. M. Umstead, A. Lawanprasert, B. Klein, S. Almarzooqi, E. S. Halstead, S. H. Medina*. Extracellular Matrix-Inspired Inhalable Aerogels for Rapid Clearance of Pulmonary Tuberculosis. Biomaterials. 2021, 273: 120848.
A. W. Simonson, A. S. Mongia, M. R. Aronson, J. N. Alumasa, D. C. Chan, A. Lawanprasert, M. D. Howe, A. Bolotsky, T. K. Mal, C. George, A. Ebrahimi, A. D. Baughn, E. A. Proctor, K. C. Keiler, S. H. Medina*. Pathogen-specific antimicrobials engineered de novo through membrane-protein biomimicry. Nature Biomedical Engineering. 2021.
A. W. Simonson, A. Lawanprasert, T. D. P. Goralski, K. C. Keiler, S. H. Medina*. Bioresponsive Peptide-Polysaccharide Nanogels – A Versatile Delivery System to Augment the Utility of Bioactive Cargo. Nanomedicine. 2019, 17: 391-400.
Re-Engineering Biomolecules to Create Adaptive Matter
Nature has evolved several elegant strategies to organize inert building blocks into adaptive supramolecular structures. Favored among these is self-assembly, where intermolecular organization of biomolecules yields unique structural, kinetic, thermodynamic, and chemical properties that are only realized in the hierarchical state. By exploiting these phenomena, our lab is developing bio-responsive nano-carriers designed to mimic the versatile and reactive behavior of natural biologic systems. In other work, we are building beyond biology by using non‐canonical amino acids to construct materials with structural states and biochemical functions that are not accessible by using natural building blocks. Through these approaches we are developing biomaterial scaffolds around which new biosensing, environmental remediation, energy harvesting and catalysis technologies are created.
