Publications by Sonia Antoranz Contera


Communication is central to the mission of science

Nature Reviews Materials Nature (2021)

S Antoranz Contera

The future of our species and planet hinges on our scientific creativity to tackle future challenges. However, the trust of the public in scientific processes needs to be earned and kept, which will require inclusive, self-reflecting, honest and inspiring science communication.


Mapping cellular nanoscale viscoelasticity and relaxation times relevant to growth of living Arabidopsis thaliana plants using multifrequency AFM

Acta Biomaterialia Elsevier 121 (2020) 371-382

J Seifert, C Kirchhelle, I Moore, S Contera

The shapes of living organisms are formed and maintained by precise control in time and space of growth, which is achieved by dynamically fine-tuning the mechanical (viscous and elastic) properties of their hierarchically built structures from the nanometer up. Most organisms on Earth including plants grow by yield (under pressure) of cell walls (bio-polymeric matrices equivalent to extracellular matrix in animal tissues) whose underlying nanoscale viscoelastic properties remain unknown. Multifrequency atomic force microscopy (AFM) techniques exist that are able to map properties to a small subgroup of linear viscoelastic materials (those obeying the Kelvin-Voigt model), but are not applicable to growing materials, and hence are of limited interest to most biological situations. Here, we extend existing dynamic AFM methods to image linear viscoelastic behaviour in general, and relaxation times of cells of multicellular organisms in vivo with nanoscale resolution (~80 nm pixel size in this study), featuring a simple method to test the validity of the mechanical model used to interpret the data. We use this technique to image cells at the surface of living Arabidopsis thaliana hypocotyls to obtain topographical maps of storage E′ = 120–200 MPa and loss E″ = 46–111 MPa moduli as well as relaxation times τ = 2.2–2.7 µs of their cell walls. Our results demonstrate that (taken together with previous studies) cell walls, despite their complex molecular composition, display a striking continuity of simple, linear, viscoelastic behaviour across scales–following almost perfectly the standard linear solid model–with characteristic nanometer scale patterns of relaxation times, elasticity and viscosity, whose values correlate linearly with the speed of macroscopic growth. We show that the time-scales probed by dynamic AFM experiments (microseconds) are key to understand macroscopic scale dynamics (e.g. growth) as predicted by physics of polymer dynamics.


Reconfigurable T‐junction DNA origami

Angewandte Chemie International Edition Wiley 59 (2020) 15942-15946

K Young, B Najafi, W Sant, S Contera, A Louis, J Doye, A Turberfield, J Bath

DNA self‐assembly allows the construction of nanometre‐scale structures and devices. Structures with thousands of unique components are routinely assembled in good yield. Experimental progress has been rapid, based largely on empirical design rules. Here we demonstrate a DNA origami technique designed as a model system with which to explore the mechanism of assembly. The origami fold is controlled through single‐stranded loops embedded in a double‐stranded DNA template and is programmed by a set of double‐stranded linkers that specify pairwise interactions between loop sequences. Assembly is via T‐junctions formed by hybridization of single‐stranded overhangs on the linkers with the loops. The sequence of loops on the template and the set of interaction rules embodied in the linkers can be reconfigured with ease. We show that a set of just two interaction rules can be used to assemble simple T‐junction origami motifs and that assembly can be performed at room temperature.


Reconfigurable T‐junction DNA origami

Angewandte Chemie Wiley (2020) ange.202006281

K Young, B Najafi, W Sant, S Contera, A Louis, J Doye, A Turberfield, J Bath


Correction to 'Bioelectrical understanding and engineering of cell biology'.

Journal of the Royal Society, Interface 17 (2020) ARTN 20200435

Z Schofield, GN Meloni, P Tran, C Zerfass, G Sena, Y Hayashi, M Grant, SA Contera, SD Minteer, M Kim, A Prindle, PRF Rocha, MBA Djamgoz, T Pilizota, PR Unwin, M Asally, OS Soyer


Biophysical characterization of DNA origami nanostructures reveals inaccessibility to intercalation binding sites

Nanotechnology IOP Publishing 31 (2020) 23

H Miller, S Antoranz Contera, A Wollman, A Hirst, KE Dunn, S Schroeter, D O'Connell, M Leake

Intercalation of drug molecules into synthetic DNA nanostructures formed through self-assembled origami has been postulated as a valuable future method for targeted drug delivery. This is due to the excellent biocompatibility of synthetic DNA nanostructures, and high potential for flexible programmability including facile drug release into or near to target cells. Such favourable properties may enable high initial loading and efficient release for a predictable number of drug molecules per nanostructure carrier, important for efficient delivery of safe and effective drug doses to minimise non-specific release away from target cells. However, basic questions remain as to how intercalation-mediated loading depends on the DNA carrier structure. Here we use the interaction of dyes YOYO-1 and acridine orange with a tightly-packed 2D DNA origami tile as a simple model system to investigate intercalation-mediated loading. We employed multiple biophysical techniques including single-molecule fluorescence microscopy, atomic force microscopy, gel electrophoresis and controllable damage using low temperature plasma on synthetic DNA origami samples. Our results indicate that not all potential DNA binding sites are accessible for dye intercalation, which has implications for future DNA nanostructures designed for targeted drug delivery.


Bioelectrical understanding and engineering of cell biology

Journal of The Royal Society Interface The Royal Society 17 (2020) 20200013

Z Schofield, GN Meloni, P Tran, C Zerfass, G Sena, Y Hayashi, M Grant, SA Contera, SD Minteer, M Kim, A Prindle, P Rocha, MBA Djamgoz, T Pilizota, PR Unwin, M Asally, OS Soyer

The last five decades of molecular and systems biology research have provided unprecedented insights into the molecular and genetic basis of many cellular processes. Despite these insights, however, it is arguable that there is still only limited predictive understanding of cell behaviours. In particular, the basis of heterogeneity in single-cell behaviour and the initiation of many different metabolic, transcriptional or mechanical responses to environmental stimuli remain largely unexplained. To go beyond the status quo, the understanding of cell behaviours emerging from molecular genetics must be complemented with physical and physiological ones, focusing on the intracellular and extracellular conditions within and around cells. Here, we argue that such a combination of genetics, physics and physiology can be grounded on a bioelectrical conceptualization of cells. We motivate the reasoning behind such a proposal and describe examples where a bioelectrical view has been shown to, or can, provide predictive biological understanding. In addition, we discuss how this view opens up novel ways to control cell behaviours by electrical and electrochemical means, setting the stage for the emergence of bioelectrical engineering.


Mapping cellular nanoscale viscoelasticity and relaxation times relevant to growth of living Arabidopsis thaliana plants using multifrequency AFM

Acta Biomaterialia (2020)

J Seifert, C Kirchhelle, I Moore, S Contera

© 2020 The shapes of living organisms are formed and maintained by precise control in time and space of growth, which is achieved by dynamically fine-tuning the mechanical (viscous and elastic) properties of their hierarchically built structures from the nanometer up. Most organisms on Earth including plants grow by yield (under pressure) of cell walls (bio-polymeric matrices equivalent to extracellular matrix in animal tissues) whose underlying nanoscale viscoelastic properties remain unknown. Multifrequency atomic force microscopy (AFM) techniques exist that are able to map properties to a small subgroup of linear viscoelastic materials (those obeying the Kelvin-Voigt model), but are not applicable to growing materials, and hence are of limited interest to most biological situations. Here, we extend existing dynamic AFM methods to image linear viscoelastic behaviour in general, and relaxation times of cells of multicellular organisms in vivo with nanoscale resolution (~80 nm pixel size in this study), featuring a simple method to test the validity of the mechanical model used to interpret the data. We use this technique to image cells at the surface of living Arabidopsis thaliana hypocotyls to obtain topographical maps of storage E′ = 120–200 MPa and loss E″ = 46–111 MPa moduli as well as relaxation times τ = 2.2–2.7 µs of their cell walls. Our results demonstrate that (taken together with previous studies) cell walls, despite their complex molecular composition, display a striking continuity of simple, linear, viscoelastic behaviour across scales–following almost perfectly the standard linear solid model–with characteristic nanometer scale patterns of relaxation times, elasticity and viscosity, whose values correlate linearly with the speed of macroscopic growth. We show that the time-scales probed by dynamic AFM experiments (microseconds) are key to understand macroscopic scale dynamics (e.g. growth) as predicted by physics of polymer dynamics.


AFM nanoindentation reveals decrease of elastic modulus of lipid bilayers near freezing point of water

Scientific Reports Nature Research 9 (2019) 19473

C Gabbutt, W Shen, J Seifert, S Antoranz Contera


Polymeric microellipsoids with programmed magnetic anisotropy for controlled rotation using low (≈10 mT) magnetic fields

Applied Materials Today Elsevier 18 (2019) 100511

A Bonilla Brunner, I Llorente Garcia, B Jang, M Amano Patino, V Alimchandani, BJ Nelson, S Pane, S Antoranz Contera

Polymeric magnetic spherical microparticles are employed as sensors/actuators in lab-on-a-chip applications, small-scale robotics and biomedical/biophysical assays. Achieving controlled stable motion of the microparticles in a fluid environment using low intensity magnetic fields is necessary to achieve much of their technological potential; this requires that the microparticle is magnetically anisotropic, which is difficult to achieve in spheres. Here we have developed a simple method to synthesise anisotropic ellipsoidal microparticles (average eccentricity 0.60 ± 0.14) by applying a magnetic field during synthesis, using a nanocomposite of polycaprolactone (PCL) with Fe3O4 nanowires. The “microellipsoids” are thoroughly characterised using optical microscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDX). Their suitability for magnetically controlled motion is demonstrated by analysing their rotation in low magnetic fields (0.1, 1, 5, 10 and 20 mT) at varying rotational frequencies (1 Hz and 5 Hz). The microellipsoids are able to follow smoothly and continuously the magnetic field, while commercial spherical particles fail to continuously follow the magnetic field, and oscillate backwards and forwards resulting in much lower average angular speeds. Furthermore, only 23 % of commercial particles analysed rotated at 1 Hz and 26 % at 5 Hz, whereas 77 % of our ellipsoidal particles rotated at 1 Hz, and 74 % did at 5 Hz.


Nano Comes to Life How Nanotechnology Is Transforming Medicine and the Future of Biology

Princeton University Press, 2019

S Contera

Embracing Biology's Complexity, At Last -- Learning by Making: DNA and Protein Nanotechnology -- Nano in Medicine -- Recreating Tissues and Organs -- Conclusions : Life Changes Everything.


Electrophysiological-mechanical coupling in the neuronal membrane and its role in ultrasound neuromodulation and general anaesthesia

Acta Biomaterialia Elsevier 97 (2019) 116-140

A Jerusalem, Z Al-Rekabi, H Chen, A Ercole, M Malboubi, M Tamayo-Elizalde, L Verhagen, S Contera

The current understanding of the role of the cell membrane is in a state of flux. Recent experiments show that conventional models, considering only electrophysiological properties of a passive membrane, are incomplete. The neuronal membrane is an active structure with mechanical properties that modulate electrophysiology. Protein transport, lipid bilayer phase, membrane pressure and stiffness can all influence membrane capacitance and action potential propagation. A mounting body of evidence indicates that neuronal mechanics and electrophysiology are coupled, and together shape the membrane potential in tight coordination with other physical properties. In this review, we summarise recent updates concerning electrophysiological-mechanical coupling in neuronal function. In particular, we aim at making the link with two relevant yet often disconnected fields with strong clinical potential: the use of mechanical vibrations—ultrasound—to alter the electrophysiogical state of neurons, e.g., in neuromodulation, and the theories attempting to explain the action of general anaesthetics.


Atomic force microscopy-indentation demonstrates that alginate beads are mechanically stable under cell culture conditions

Journal of the Mechanical Behavior of Biomedical Materials Elsevier 93 (2019) 61-69

C Chui, A Bonilla-Brunner, J Seifert, S Contera, H Ye

Alginate microbeads are extensively used in tissue engineering as microcarriers and cell encapsulation vessels. In this study, we used atomic force microscopy (AFM) based indentation using 20 µm colloidal probes to assess the local reduced elastic modulus (E * ) using a novel method to detect the contact point based on the principle of virtual work, to measure microbead mechanical stability under cell culture conditions for 2 weeks. The bead diameter and swelling were assessed in parallel. Alginate beads swelled up to 150% of their original diameter following addition of cell culture media. The diameter eventually stabilized from day 2 onwards. This behaviour was mirrored in E * where a significant decrease was observed at the start of the culture period before stabilization was observed at ~ 2.1 kPa. Furthermore, the mechanical properties of freeze dried alginate beads after re-swelling them in culture media were measured. These beads displayed vastly different structural and mechanical properties compared those that did not go through the freeze drying process, with around 125% swelling and a significantly higher E * at values over 3 kPa.


A simple mathematical model of allometric exponential growth describes the early three-dimensional growth dynamics of secondary xylem in Arabidopsis roots

Royal Society Open Science The Royal Society 6 (2019) 190126-190126

A Thamm, S Sanegre-Sans, J Paisley, S Meader, A Milhinhos, S ANTORANZ CONTERA, J Agusti


Author Correction: How to probe the spin contribution to momentum relaxation in topological insulators.

Nature communications (2018)

MOON-SUN Nam, B Williams, YULIN Chen, S Contera, S Yao, M Lu, YULIN Chen, GA Timco, CA Muryn, ARZHANG Ardavan

The original version of this Article contained an error in the spelling of the author Benjamin H. Williams, which was incorrectly given as Benjamin H. Willams. This has now been corrected in both the PDF and HTML versions of the Article.


How to probe the spin contribution to momentum relaxation in topological insulators

Nature Communications Springer Nature 9 (2018) 56

M-S Nam, BH Williams, Y Chen, S Antoranz Contera, S Yao, M Lu, Y-F Chen, GA Timco, CA Muryn, Winpenny, A Ardavan

Topological insulators exhibit a metallic surface state in which the directions of the carriers’ momentum and spin are locked together. This characteristic property, which lies at the heart of proposed applications of topological insulators, protects carriers in the surface state from back-scattering unless the scattering centres are time-reversal symmetry breaking (i.e. magnetic). Here, we introduce a method of probing the effect of magnetic scattering by decorating the surface of topological insulators with molecules whose magnetic degrees of freedom can be engineered independently of their electrostatic structure. We show that this approach allows us to separate the effects of magnetic and non-magnetic scattering in the perturbative limit. We thereby confirm that the low-temperature conductivity of SmB6 is dominated by a surface state and that the momentum of quasiparticles in this state is particularly sensitive to magnetic scatterers, as expected in a topological insulator.


Multifrequency AFM reveals lipid membrane mechanical properties and the effect of cholesterol in modulating viscoelasticity

Proceedings of the National Academy of Sciences National Academy of Sciences 115 (2018) 2658-2663

Z Al Rekabi, S Contera

<p>The physical properties of lipid bilayers comprising the cell membrane occupy the current spotlight of membrane biology. Their traditional representation as a passive 2D fluid has gradually been abandoned in favor of a more complex picture: an anisotropic time-dependent viscoelastic biphasic material, capable of transmitting or attenuating mechanical forces that regulate biological processes. In establishing new models, quantitative experiments are necessary when attempting to develop suitable techniques for dynamic measurements. Here, we map both the elastic and viscous properties of the model system 1,2-dipalmitoyl-<em>sn</em>-glycero-3-phosphocholine (DPPC) lipid bilayers using multifrequency atomic force microscopy (AFM), namely amplitude modulation–frequency modulation (AM–FM) AFM imaging in an aqueous environment. Furthermore, we investigate the effect of cholesterol (Chol) on the DPPC bilayer in concentrations from 0 to 60%. The AM–AFM quantitative maps demonstrate that at low Chol concentrations, the lipid bilayer displays a distinct phase separation and is elastic, whereas at higher Chol concentration, the bilayer appears homogenous and exhibits both elastic and viscous properties. At low-Chol contents, the <em>E</em><sub>storage</sub> modulus (elastic) dominates. As the Chol insertions increases, higher energy is dissipated; and although the bilayer stiffens (increase in <em>E</em><sub>storage</sub>), the viscous component dominates (<em>E</em><sub>loss</sub>). Our results provide evidence that the lipid bilayer exhibits both elastic and viscous properties that are modulated by the presence of Chol, which may affect the propagation (elastic) or attenuation (viscous) of mechanical signals across the cell membrane.</p>


Amphiphilic DNA tiles for controlled insertion and 2D assembly on fluid lipid membranes: Effect on mechanical properties

Nanoscale Royal Society of Chemistry 9 (2017) 3051-3058

C Dohno, S Makishi, K Nakatani, S Antoranz Contera

Future lipid membrane-associated DNA nanostructures are expected to find applications ranging from synthetic biology to nanomedicine. Here we have designed and synthesized DNA tiles and modified them by amphiphilic covalent moieties. dod-DEG groups, which consist of a hydrophilic diethylene glycol (DEG) and a hydrophobic dodecyl group, are introduced at the phosphate backbone to create amphiphilic DNA strands which are subsequently introduced into one face of DNA tiles. In this way the tile becomes able to stably bind to lipid membranes by insertion of the hydrophobic groups inside the bilayer core. The functionalized tiles do not aggregate in solution. Our results show that these amphiphilic DNA tiles can bind and assemble into 2D lattices on both gel and fluid lipid bilayers. The binding of the DNA structures to membranes is dependent on the lipid phase of the membrane, the concentration of Mg2+ cation, the length of the amphiphilic modifications to the DNA as well as on the density of the modifications within the tile. Atomic force microscopy–based force spectroscopy is used to investigate the effect of the inserted DNA tiles on the mechanical properties of the lipid membranes. The results indicate that the insertion of DNA tiles produces an approx. 20% increase of the bilayer breakthrough force.


Magneto-electrical orientation of lipid-coated graphitic micro-particles in solution

RSC Advances Royal Society of Chemistry (RSC) 6 (2016) 46643-46653

J Nguyen, S Contera, I Llorente García

<p>We demonstrate, for the first time, confinement of the orientation of graphitic micro-flakes to a well-defined plane in solution by applying two perpendicular fields: a vertical static magnetic field and a horizontal time-varying electric field.</p>


Designer cantilevers for even more accurate quantitative measurements of biological systems with multifrequency AFM

Nanotechnology IOP Publishing 27 (2016) 132501-132501

S Contera

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