NANO COMES TO LIFE: How Nanotechnology is Transforming Medicine and the Future of Biology
Abstract:
Nano Comes to Life opens a window onto the nanoscale-the infinitesimal realm of proteins and DNA where physics and cellular and molecular biology meet-and introduces readers to the rapidly evolving nanotechnologies that are allowing us to manipulate the very building blocks of life. Sonia Contera gives an insider’s perspective on this new frontier, revealing how nanotechnology enables a new kind of multidisciplinary science that is poised to give us control over our own biology, our health, and our lives. Drawing on her perspective as one of today’s leading researchers in the field, Contera describes the exciting ways in which nanotechnology makes it possible to understand, interact with, and manipulate biology-such as by designing and building artificial structures and even machines at the nanoscale using DNA, proteins, and other biological molecules as materials. In turn, nanotechnology is revolutionizing medicine in ways that will have profound effects on our health and longevity, from nanoscale machines that can target individual cancer cells and deliver drugs more effectively, to nanoantibiotics that can fight resistant bacteria, to the engineering of tissues and organs for research, drug discovery, and transplantation. The future will bring about the continued fusion of nanotechnology with biology, physics, medicine, and cutting-edge fields like robotics and artificial intelligence, ushering us into a new “transmaterial era.” As we contemplate the power, advantages, and risks of accessing and manipulating our own biology, Contera offers insight and hope that we may all share in the benefits of this revolutionary research.Biophysical characterization of DNA origami nanostructures reveals inaccessibility to intercalation binding sites
Abstract:
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.Multifrequency AFM reveals lipid membrane mechanical properties and the effect of cholesterol in modulating viscoelasticity
Abstract:
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-sn-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 Estorage modulus (elastic) dominates. As the Chol insertions increases, higher energy is dissipated; and although the bilayer stiffens (increase in Estorage), the viscous component dominates (Eloss). 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.