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Talk by Jurriaan Huskens

Title: "“Superselectivity and receptor recruitment as organizing principles in bio sensing and self assembly”"
Occasion: GDCh-Kolloquium
Start: 21.11.2023 - 17:00
Location: CellNanOs, 38/201

About the speaker: Prof. Dr. ir. Jurriaan Huskens conducts research on Supramolecular Chemistry and Molecular Nanofabrication at the University of Twente, Netherlands.

Abstract of the talk: Multivalent interactions govern biological processes like cell signaling and virus
infections. Such interactions are characterized by unique energetic, structural and
dynamic properties, and they occur at a well defined contact area, in which multiple
complementary binding sites interact with each other in a reversible and dynamic
manner. Emerging properties of such systems are superselectivity and recruitment.
Superselectivity describes the nonlinear dependence of binding with receptor/ligand
densities, whereas recruitment occurs when mobility allows receptor and/or ligand sites
to move in and out of the contact area, typically leading to enhanced binding sites
occurring within the contact area and depletion thereof outside. The present report
shows how superselectivity and recruitment can be engineered to create new principles
for biomarker isolation and for materials self assembly, respectively.

In the first example, superselectivity is employed to up concentrate the cancer
biomarker hypermethylated DNA (hmDNA). Surfaces with controlled densities of a
methyl binding domain (MBD) protein show enhanced affinity for DNA with increasing
numbers of methylation sites. This allows implementation into a microfluidic device in
which hmDNA can be effectively isolated from liquid biopsies to allow highly sensitive
detection.

In the second example, recruitment is shown to provide stoichiometrically controlled
assemblies of vesicles decorated with complementary receptor and ligand sites
implemented in their membranes. The affinity between the vesicles shows signs of
superselectivity while receptor/ligand recruitment controls the binding stoichiometry of
the vesicles. Fluorescence resonance energy transfer (FRET) of dyes incorporated
within the vesicle membranes allows detailed analysis of the contact area between
them. Overall, these examples underline the powerful paradigm of multivalent
interactions and their functional properties.