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David M. Smith

Fraunhofer Institute for Cell Therapy and Immunology

ORCID: 0000-0002-8344-850X

Publishes on Advanced biosensing and bioanalysis techniques, Cellular Mechanics and Interactions, RNA Interference and Gene Delivery. 80 papers and 1.5k citations.

80Publications
1.5kTotal Citations

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Top publicationsby citations

Chiral plasmonic DNA nanostructures with switchable circular dichroism
Robert Schreiber, Ngoc Luong, Zhiyuan Fan et al.|Nature Communications|2013
Cited by 333Open Access

Circular dichroism spectra of naturally occurring molecules and also of synthetic chiral arrangements of plasmonic particles often exhibit characteristic bisignate shapes. Such spectra consist of peaks next to dips (or vice versa) and result from the superposition of signals originating from many individual chiral objects oriented randomly in solution. Here we show that by first aligning and then toggling the orientation of DNA-origami-scaffolded nanoparticle helices attached to a substrate, we are able to reversibly switch the optical response between two distinct circular dichroism spectra corresponding to either perpendicular or parallel helix orientation with respect to the light beam. The observed directional circular dichroism of our switchable plasmonic material is in good agreement with predictions based on dipole approximation theory. Such dynamic metamaterials introduce functionality into soft matter-based optical devices and may enable novel data storage schemes or signal modulators. Plasmonic resonances in nanoparticle helices arranged by the DNA origami method can give rise to strong circular dichroism at visible wavelengths. Schreiber et al. show that aligning and then toggling the orientation of such nanoparticle helices enables reversible switching of the dichroic response.

Jamming transitions in cancer
Linda Oswald, Steffen Grosser, David M. Smith et al.|Journal of Physics D Applied Physics|2017
Cited by 180Open Access

The traditional picture of tissues, where they are treated as liquids defined by properties such as surface tension or viscosity has been redefined during the last few decades by the more fundamental question: under which conditions do tissues display liquid-like or solid-like behaviour? As a result, basic concepts arising from the treatment of tissues as solid matter, such as cellular jamming and glassy tissues, have shifted into the current focus of biophysical research. Here, we review recent works examining the phase states of tissue with an emphasis on jamming transitions in cancer. When metastasis occurs, cells gain the ability to leave the primary tumour and infiltrate other parts of the body. Recent studies have shown that a linkage between an unjamming transition and tumour progression indeed exists, which could be of importance when designing surgery and treatment approaches for cancer patients.

Nucleic Acid Nanostructures for Biomedical Applications
Cited by 73

We review the current developments of DNA-based nanostructures for drug delivery, immunotherapy, diagnostics and molecular biology. DNA is a powerful building block, which by the nature of predictable base pairing, allows the creation of molecular scaffolds, cages and multifunctional carriers with nanoscale dimensions. These engineered constructs have unsurpassed structural qualities such as full control over size, shape and dispersity. Site-specific surface modification enables the presentation of biomolecules at defined distances and stochiometries, which allows tailored cell targeting and substance delivery on demand. As the first successful in vivo applications of DNA nanostructures have recently been demonstrated, we now expect a burst of biomedical studies involving this rapidly progressing technology.

Force-Induced Unravelling of DNA Origami
Cited by 69Open Access

The mechanical properties of DNA nanostructures are of widespread interest as applications that exploit their stability under constant or intermittent external forces become increasingly common. We explore the force response of DNA origami in comprehensive detail by combining AFM single molecule force spectroscopy experiments with simulations using oxDNA, a coarse-grained model of DNA at the nucleotide level, to study the unravelling of an iconic origami system: the Rothemund tile. We contrast the force-induced melting of the tile with simulations of an origami 10-helix bundle. Finally, we simulate a recently proposed origami biosensor, whose function takes advantage of origami behavior under tension. We observe characteristic stick-slip unfolding dynamics in our force-extension curves for both the Rothemund tile and the helix bundle and reasonable agreement with experimentally observed rupture forces for these systems. Our results highlight the effect of design on force response: we observe regular, modular unfolding for the Rothemund tile that contrasts with strain-softening of the 10-helix bundle which leads to catastropic failure under monotonically increasing force. Further, unravelling occurs straightforwardly from the scaffold ends inward for the Rothemund tile, while the helix bundle unfolds more nonlinearly. The detailed visualization of the yielding events provided by simulation allows preferred pathways through the complex unfolding free-energy landscape to be mapped, as a key factor in determining relative barrier heights is the extensional release per base pair broken. We shed light on two important questions: how stable DNA nanostructures are under external forces and what design principles can be applied to enhance stability.