In many biological processes, dynamic interactions and multivalency play a crucial role. This is particularly true for interactions at the cell membrane which is by itself a highly dynamic, multivalent ligand platform. Many biological interaction are not (fully) understood. For example: how many interactions are needed for a virus to be endocytosed? How do cells sense the dynamics of its environment and what is the effect on cell behaviour? What is the role of receptor density, mobility and clustering? Answering these kind of questions is not just fundamentally relevant. It will also aid in the design of biosensors, provide more control in tissue engineering and help the development of multivalent constructs for cell targeting and pathogen inhibition. Here, we employ a supramolecular surface modification method that allow for dynamic interactions with biological entities ranging from small molecules, to vesicles, viruses, and finally to cells. The surface modification consists of a functionalized supported lipid bilayer. This well-known cell membrane mimic also provides ease of preparation, controlled functionalization and non-fouling properties. Here, we have used these qualities to (1) probe the effect of receptor affinity on cell behaviour using lipidated “RGD” peptides (2) study interaction characteristics of an influenza virus model and (3) design a vesicle-based system that targets not only based on receptor type but also based on receptor density (i.e. superselectivity). First, we characterize the fabrication of the interaction platform. Then, we demonstrate that (1) the synthesized library of lipidated RGD peptides has affinities ranging over 3 orders of magnitude for the lipid bilayer and that cells sense these differences and alter their behaviour accordingly; (2) the supported lipid bilayer can be employed as a powerful platform to quantitatively investigate virus binding; (3) superselective targeting of liposomes to supported lipid bilayers displaying laterally mobile ligands was achieved. In these studies, read-out was performed using surface sensitive techniques (QCM-D, ellipsometry, fluorescence microscopy and flow cytometry) and cell studies (fixed and live cell imaging).

Characterization of the binding of vesicles, viruses and cells to biomimetic lipid bilayers

255th National Meeting (2018)

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