Editorial on nanobiology

Cells and tissues form and function as hierarchical assemblies of nanometer scale components. Methods are currently developed for synthesizing complex particles in the mesoscopic size range of 10–100 nm. They offer a palette of original materials that are becoming available with a wide variety of new optical, electronic, magnetic and structural properties which are not available either from their individual atomic or molecular components or from bulk solids. Nanobiology arises from the interplay between fundamental or applied researches in nano-material science and their biological or medical applications. This themed issue of PCCP provides an overview of the way nanobiology is establishing bridges between physical chemistry and biology towards medicine with broad applications to molecular imaging, molecular diagnosis, and targeted therapy.

Biomolecules are characterized by their exquisite specific recognition abilities, thanks to the establishment of weak interactions such as van der Waals or hydrogen bonds at rather short distances. In this issue, the Perspective written by A. G. Cherstvy (DOI: 10.1039/c0cp02796k) highlights the role of electrostatic forces on different scales of DNA organization. This ranges from the high speed of transcription factors for scanning DNA and precisely recognizing sequences up to interactions between nucleosomes, compaction of chromatin and DNA encapsulation in viral capsids. This Perspective provides a general theoretical framework for rationalizing the structural properties of DNA-related systems imposed by intermolecular forces even in the case of very large systems inaccessible to computer simulations. The role of inhomogeneous electric fields upon nano-particles localization (dielectrophoresis) is demonstrated by S. Strobel et al. (DOI: 10.1039/c0cp02718a). DNA-coated gold nanoparticles are trapped in nanogaps with inter-electrode distances of only 13 nm. This opens the route to the fabrication of miniaturized biosensors using nano-fabrication techniques developed by the micro-electronic industry. Conversely, the strong need for further miniaturization of electronic devices receives help from the ability of DNA to create arbitrary two- and three-dimensional designed nanostructures. P. F. Xu et al. (DOI: 10.1039/c0cp02815k) demonstrate how single-wall carbon nanotubes (CNT) can be assembled on surfaces. Part of the DNA sequences adhere and solubilize the CNTs while the other part anchors them on surfaces. Surfaces patterned by specifically hybridized DNA sequences drive absorption, binding and alignmement of CNTs directly from solution, providing openings towards future use of carbon nanotubes in electronics.

Nanoparticles can be linked with ligands used to target diseased organs or tumors with high affinity and specificity. Among ligands, peptide drugs face enzymatic breakdown along their course. The use of un-natural aminoacids is a powerful mean for deceiving proteases but must not modify the bioactivity. G. Revilla-López et al. (DOI: 10.1039/c0cp02572K) employ molecular dynamics simulations for engineering a tumor-homing pentapeptide tethered to the surface of a nanoparticle. They demonstrate that the inclusion of a new aminoacid both protects from proteolysis and stabilizes the bioactive conformation. The power of single-molecule spectroscopy is highlighted by the deciphering of the mechanism governing action of an enzyme. The reverse gyrase investigated by Y. Toro Duany and D. Klostermeier (DOI: 10.1039/c0cp02859b) introduces positive supercoils in DNA. It senses single-strand DNA and protects DNA against thermal damages at high temperature. It is a complex biomolecule comprising two main components, a helicase-like separating annealed DNA strands and a topoisomerase modifying the winding. The use of single-molecule Förster resonance energy transfer (FRET) provides a structural understanding of conformational changes in the helicase domain cooperating with the topoisomerase domain leading to the enzymatic topological activity.

In order to avoid side effects, drugs can be trapped in nano-containers that only deliver their cargo to the target through controlled opening of a nanovalve. F. Porta et al. (DOI: 10.1039/c0cp02959) present the use of oligopeptides as part of a nanovalve system in peptide modified mesoporous (a few nm) silica nanocontainers that are highly biocompatible. Those peptides are derived from a larger peptide issued from the HIV and easily penetrate cells. The release of the drug then occurs when the bond linking the drug and the peptide is cleaved under chemical conditions reigning in the cell cytoplasm. In addition to drug delivery devices, polymeric fibers can be used for tissue engineering and regenerative medicine. Chitosan (deacylated chitin) is an attractive component for its biocompatibility. A. Cooper et al. (DOI: 10.1039/c0cp02909b) propose a manufacturing procedure of nanofibers that remain stable in an aqueous environment. The cross-linking between the oligosaccharide chitosan and lactic acid allows the use of electrospinning for production of nanofibers that might be usable for nerve tissue regeneration.

External forces can be applied to biomolecules by means of optically-controlled thermal gradients. In a Perspective devoted to transport and guiding of liquids on the micrometer scale, F. M. Weinert et al. (DOI: 10.1039/c0cp02359k) present the theoretical basis of thermophoresis and its applications to creation of light-driven microfluidic flow in water or in ice. Examples of the potential of the method are provided such as new binding assays of inhibitors of kinases and replication of DNA molecules and their active storage against diffusion in micrometer-size traps.

Detection of fluorescent light issued from molecular probes is one of the most popular methods used in biomolecular imaging. An uncontrolled environment of the used fluorophores lead to their parasitic quenching and should be avoided as much as possible. This can be achieved by using gold nanoparticle (AuNP) fluorescence-based activatable probes that are described in the Perspective of M. Swierczewska et al. (DOI: 10.1039/c0cp02967j). Different theories for describing energy transfer according to the distance between fluorophores and the metallic nanoparticles are presented. They find applications in the use of molecular beacons that comprise an oligonucleotide probe capable to hybridize with a specific DNA or RNA sequence. AuNP can also be functionalized and bind to fluorophores leading to complexes capable of specifically recognizing proteins. New array-based sensor platforms can then be designed. Those “chemical noses” can for example differentiate bacteria or discriminate between healthy and cancerous cells.

Among the nanoparticles, AuNPs receive great attention due to their ease of functionalization, their biocompatibility and their plasmon resonance widely tunable by changing dimensions and shape. X. Hu et al. (DOI: 10.1039/c0cp02434a) investigate coating of gold nanorods. Gold nanorods are particularly efficient at converting optical energy into heat and are thus used to deliver intense photothermal effects with subcellular precision. For practical applications, the coating material must be carefully designed in order to prevent aggregation, dissipate heat created from laser irradiation before gold melting while still maintaining low toxicity. When suitably functionalized, for example with RNA aptamers, the obtained coated AuNPs can target tumor cells that can then be destroyed by photothermal therapy. Using coated magnetic nanoparticles, F. Benyettou et al. (DOI: 10.1039/c0cp02034f) demonstrate how several complementary functions can be fulfilled. Superparamagnetic γFe₂O₃ particles used as magnetic resonance imaging contrasting agents can be coated with molecules reducing cancer cell viability and fluorophores allowing the monitoring of cell uptake by means of fluorescence microscopy. The therapeutic efficiency can be tested in vivo, thanks to the magnetic properties of the nanoparticles. The application of an external magnetic field gradient increases their retention in the vicinity of tumor volumes avoiding the spread of toxicity over a whole living body.

Cell membranes are compartimentalized into small domains, called rafts, with a different composition. Their observation requires sub-diffraction microscopy techniques. L. Opilik et al. (DOI: 10.1039/c0cp02832k) combine atomic force microscopy (AFM) and tip-enhanced Raman spectroscopy to obtain both images with an excellent spatial resolution and the label-free chemical information concerning the rafts. Y. Hu and coworkers (DOI: 10.1039/c0cp02800b) use AFM for mapping surface properties of bacteria likely to form harmfull biofilms through adhesion to surfaces. These studies prove that AFM can be useful in the search for molecular inhibitors of biofilm formation that are added during the bacterial growth phase.

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