MODEL SYSTEMS TO UNDERSTAND COMPLEX MULTIVALENCY

Multivalency is a key feature of many biological phenomena, from immune activation to cell adhesion on extracellular matrix. Matching receptor spacing with that of presented ligands could lead to enhanced specificity and selectivity of therapeutic and diagnostic agents. Recently, the field of DNA nanotechnology emerged as means to design particles that can spatially control ligand presentation with unprecedented nanoscale precision. To design controlled binding experiments with precise receptor spacing and ligand spacing as variables, in silico modelling of particles, surface composition and binding kinetics are fundamental. The aim of this work consists in the development of elaborate analytical models of receptor spacing over flat surfaces and the combination with molecular simulations of the ligand presenting particles. In particular, simulations include atomistic molecular dynamics of four different nanoparticles and molecular docking of the former with the receptor surface of interest. The analytical models of the surfaces allow for simulation in the presence of one or two species of receptors simultaneously and the visualization of the corresponding surface organization. The data is then used as input for experimental design development. Based on the results obtained in this thesis, it is possible to describe the complete interaction landscape formed by multivalent DNA nanoparticles with immobilized surface receptors. It gives insights in the flexibility of the structures and their steric constraints in surface interactions. This knowledge allows better design of experimental parameters to evaluate the role of spatial organization of ligand and receptors in achieving specific and selective interactions.