IMX Seminar Series - Designing super-specificity with precision materials

Understanding the mechanisms, extent, and consequences of receptor co-localization and inter-receptor communication is critical for the design and development of therapeutic nanoparticles and functional biomaterial scaffolds. Nature orchestrates specificity and selectivity in receptor targeting by introducing multivalency to control binding affinities. (i) Cell-cell interactions, cell-matrix binding and immune activation all are controlled through multiple weak interactions between one or more types of ligand-receptor pairs. Materials scientists have utilized this concept to achieve targeted delivery, increased specificity and selectivity of therapeutic and diagnostic ligand-functionalized nanoparticles. Numerous ligand-presenting materials have been developed yet the translation to clinical success is limited. The main cause hereof is a lack of control in particle shape, size, ligand-spacing and ligand-number, resulting in a distribution of particles with varying functionality. Precision engineering of functional materials is required to acquire insight into these fundamental natural mechanisms.
In this talk, I aim to develop a precision-engineered materials platform to gain quantitative insights into the fundamental mechanisms of complex multivalency that lead to super-specificity. I show how the development of multivalent particles with controlled ligand spacing, heterogeneity, stoichiometry and positioning are needed to accurately study the role of these parameters in overall binding affinity on model surfaces and on the cell membrane. Together with new analysis methods, theory and simulations we aim to introduce an unmet level of accuracy and control in functional materials self-assembly and truly be super-specific.   

(i) Kiessling, L. L., Gestwicki, J. E. & Strong, L. E. Synthetic multivalent ligands as probes of signal transduction. Angew. Chem. Int. Ed Engl. 45, 2348–2368 (2006).
Bio:
Maartje Bastings studied Biomedical Engineering at the Eindhoven University of Technology (TU/e) and graduated Cum Laude in the group of Prof. E. W. “Bert” Meijer, where she continued her Ph.D. program funded by a Toptalent Fellowship from the Dutch Science Foundation (NWO), cosupervised by Dr. Patricia Y. W. Dankers. Her research focused on the understanding of multivalent binding mechanisms for directed targeting and the development of supramolecular biomaterials, and she received her Ph.D. degree in 2012. She was awarded the University Academic Award in 2013 for best Ph.D. thesis at the TU/e. She moved to the Wyss Institute of Harvard University in Boston as a NWO Rubicon and Human Frontier Science Program postdoctoral fellow in the lab of Prof. William M. Shih. She studies DNA as programmable biomaterial to design immune responses and assemble into multimodal nanoparticles. Since January 2017 she is heading the Programmable Biomaterials Laboratory as tenure track Assistant Professor in the Materials Science and Engineering Department at EPFL, Switzerland, developing novel precision-engineered materials as tools to better understand fundamental mechanisms in multivalent interactions.