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Selective integrin targeting with DNA-based nanomaterials

Eva Eugene Kurisinkal

Targeting cells specific to type and state remains a challenge in developing effective therapies, sensitive diagnostics, also robust and versatile tissue engineering. A promising strategy is to focuses on improving the inherent selectivity of the targeting system through precise orchestration of ligand-receptor interactions. Integrin receptors present themselves as a strategic target as their expression has been reported to be regulated across cell types and states. The principle of super-selectivity permits the selective targeting of integrin receptors above a threshold concentration in high valency and relative low affinity systems, leaving sparser counterparts unaffected. Here, we demonstrate that DNA based scaffolds with rigid ligand nanoscale spatial presentation can be designed to discriminate between adhesions by varying RGD ligand spacing targeting integrin âº5Î²1 receptors. We begin by modelling integrin âº5Î²1 receptors nearest neighbour distributions across HUVEC, CHO and HeLa cells. Targeting spacings in the sub-60nm reveal trends in binding efficacies based on cell type and activation state. An ensuing study of HUVEC response to local ligand geometries of varying global inter-geometry spacings presented on higher valency DNA scaffolds randomly immobilised result in two distinct adhesion cluster formations. Our findings open avenues in the design of super-selective targeting elements, besides providing insight on the regulation of integrin receptors on the cell surface across different cell types. Parameters for ligand presentation at the sub-adhesion scale affords selective cell engagement in biomaterial presentation.

EPFL2022

Engineering a stable future for DNA-origami as a biomaterial

Maartje Martina Cornelia Bastings, Hale Bila, Eva Eugene Kurisinkal

DNA as a biomaterial has evoked great interest as a potential platform for therapeutics and diagnostics and as hydrogel scaffolds due to the relative ease of programming its robust and uniform shape, site-specific functionality and controlled responsive behavior. However, for a stable self-assembled product, a relatively high cation concentration is required to prevent denaturation. Physiological and cell-culture conditions do not match these concentrations and present additional nucleases that cause a serious threat to the integrity of DNA-based materials. For the translation of this promising technology towards bioengineering challenges, stability needs to be guaranteed. Over the past years, various methods have been developed addressing the stability-related weaknesses of DNA-origami. This mini-review explains the common stability issues and compares the stabilization strategies recently developed. We present a detailed overview of each method in order to ease the selection process on which method to use for future users of DNA-origami as a biomaterial.

ROYAL SOC CHEMISTRY2019

Large‐Range HS‐AFM Imaging of DNA Self‐Assembly through In Situ Data‐Driven Control

Maartje Martina Cornelia Bastings, Charlène Cécile Geneviève Brillard, Georg Fantner, Christoph Manuel Kammer, Alireza Karimi, Eva Eugene Kurisinkal, Adrian Pascal Nievergelt

Understanding hierarchical self-assembly of biological structures requires real time measurement of the self-assembly process over a broad range of length- and timescales. The success of high-speed atomic force microscopy (HS-AFM) in imaging small scale molecular interactions has fueled attempts to introduce this method as a routine technique for studying biological and artificial self-assembly processes. Current state of the art HS-AFM scanners achieve their high imaging speed by trading achievable field of view for bandwidth. This limits their suitability when studying larger biological structures. In ambient conditions, large range scanners with lower resonance frequencies offer a solution when combined with first principle model-based schemes. For imaging molecular self-assembly process in fluid however, such traditional control techniques are less suited. In liquid, the time-varying changes in the behavior of the complex system necessitates frequent update of the compensating controller. Recent developments in data-driven control theory offer a model-free, automatable approach to compensate the complex system behavior and its changes. Here we present a data-driven control design method to extend the imaging speed of a conventional AFM tube scanner by one order of magnitude. This enabled the recording of the self-assembly process of DNA tripods into a hexagonal lattice at multiple length scales.

2019