Optimality and cooperativity in superselective surface binding by multivalent DNA nanostars

Soft Matter, vol. 20, pp. 8515–8523

Abstract

Weak multivalent interactions govern a large variety of biological processes like cell-cell adhesion and virus-host interactions. These systems distinguish sharply between surfaces based on receptor density, known as superselectivity. Present experimental studies typically involve tens or hundreds of interactions, resulting in a high entropic contribution leading to high selectivities. However, if, and if so how, systems with few ligands, such as multi-domain proteins and bacteriophages binding to their host, show superselective behavior is an open question. Here, we address this question with a multivalent experimental model system based on star shaped branched DNA nanostructures (DNA nanostars) with each branch featuring a single stranded overhang that binds to complementary receptors on a target surface. Each DNA nanostar possesses a fluorophore, to directly visualize DNA nanostar surface adsorption by total internal reflection fluorescence microscopy (TIRFM). We observe that DNA nanostars can bind superselectively to surfaces and bind optimally at a valency of three, for a given binding strength and concentration. We explain this optimum by extending the current theory with interactions between DNA nanostar binding sites (ligands). Our results add to the understanding of multivalent interactions, by identifying cooperative mechanisms that lead to optimal selectivity, and providing quantitative values for the relevant parameters. These findings inspire additional design rules which improve future work on selective targeting in directed drug delivery.

Authors 5

1. Christine Linne Aachen Soft Matter Physics Huygens-Kamerlingh Onnes Laboratory Leiden Institute of Physics (LION)

   Leiden University · Delft University of Technology

   Affiliation as printed

   Department of Bionanoscience, TU Delft, 2629 HZ Delft, The Netherlands

   Soft Matter Physics, Huygens-Kamerlingh Onnes Laboratory, Leiden Institute of Physics, 2300 RA Leiden, The Netherlands

2. E. Heemskerk

   Delft University of Technology

   Affiliation as printed

   Department of Bionanoscience, TU Delft, 2629 HZ Delft, The Netherlands

3. Jos W. Zwanikken

   Delft University of Technology

   Affiliation as printed

   Department of Bionanoscience, TU Delft, 2629 HZ Delft, The Netherlands

4. Daniela J. Kraft corresponding Aachen Soft Matter Physics Huygens-Kamerlingh Onnes Laboratory Leiden Institute of Physics (LION)

   Leiden University

   Affiliation as printed

   Soft Matter Physics, Huygens-Kamerlingh Onnes Laboratory, Leiden Institute of Physics, 2300 RA Leiden, The Netherlands

5. Liedewij Laan corresponding

   Delft University of Technology

   Affiliation as printed

   Department of Bionanoscience, TU Delft, 2629 HZ Delft, The Netherlands