Shikha Dhiman

Project title:  Adaptive Multivalency and Dynamic Reciprocity with Supramolecular Biomaterial

Host Institution: Eindhoven University of Technology (TU/e)

Host Supervisor: Prof. Dr. E. W. Meijer

Co-host Institution: Technical University of Munich (TUM)

Co-host Supervisor: Prof. Dr. Oliver Lieleg

Summary project:Nature uses an ensemble of multiple receptors to interact cooperatively via non-covalent interactions with ligands for high binding strength referred as multivalency. This is accompanied by dynamic reciprocity i.e. a synergistic bidirectional reorganization between receptors and ligands. This adaptive multivalency and dynamic recruitment are the basis for various biological phenomenon such as intercell interaction, extracellular matrix-cell interaction and communication. Moreover, the recent COVID-19 pandemic stimulated the research to understand “virus-cell transfection” which suggested the role of multivalency as mode of binding of the virus to human cells and hence multivalency determines the rate of infection. To counter this, multivalent therapeutic agents are pursued to cure several disease. Moreover, the lack of clear understanding into the mechanism of multivalency, due to unavailability of tools to deconvolute this complex phenomenon, act as barrier for high performance biomaterials. The proposal aims to employ super-resolution microscopy to investigate the crucial role of adaptive multivalency and dynamic recruitment using a supramolecular biomaterial with cell/cell-mimic. Thus, a systematic study with variation of receptor and ligand density at extraordinary spatial and temporal resolution shall probe the unprecedented insights. The receptor density cannot be regulated in a cell, thus, a model cell-membrane (Supported Lipid Bilayer) will allow this control by varying the ratio of functionalized to non-functionalized lipids. Moreover, the precise ligand density can be achieved by controlling monomer ratio in multicomponent supramolecular copolymerization. Hence, the study shall pave the way to tackle many of the exciting unforeseen challenges of supramolecular biomaterials for biomedical applications.


Shikha Dhiman