Nonbiological Environments Research Articles

Chiral Iron Oxide Supraparticles Enable Enantiomer-Dependent Tumor-Targeted Magnetic Resonance Imaging.

The chemical, physical and biological effects of chiral nanomaterials have inspired general interest and demonstrated important advantages in fundamental science. Here, chiral iron oxide supraparticles (Fe3 O4 SPs) modified by chiral penicillamine (Pen) molecules with g-factor of ≈2 × 10-3 at 415nm are fabricated, and these SPs act as high-quality magnetic resonance imaging (MRI) contrast agents. Therein, the transverse relaxation efficiency and T2 -MRI results demonstrated chiral Fe3 O4 SPs have a r2 relaxivity of 157.39 ± 2.34 mM-1 ·S-1 for D-Fe3 O4 SPs and 136.21 ± 1.26 mM-1 ·S-1 for L-Fe3 O4 SPs due to enhanced electronic transition dipole moment for D-Fe3 O4 SPs compared with L-Fe3 O4 SPs. The in vivo MRI results show that D-Fe3 O4 SPs exhibit two-fold lower contrast ratio than L-Fe3 O4 SPs, which enhances targeted enrichment in tumor tissue, such as prostate cancer, melanoma and brain glioma tumors. Notably, it is found that D-Fe3 O4 SPs have 7.7-fold higher affinity for the tumor cell surface receptor cluster-of-differentiation 47 (CD47) than L-Fe3 O4 SPs. These findings uncover that chiral Fe3 O4 SPs act as a highly effective MRI contrast agent for targeting and imaging broad tumors, thus accelerating the practical application of chiral nanomaterials and deepening the understanding of chirality in biological and non-biological environments.

Light-Powered Ion Pumping in a Cation-Selective Conducting Polymer Membrane.

The simulation of the ion pumping against a proton gradient energized by light in photosynthesis is of significant importance for the energy conversion in a non-biological environment. Herein, we report light-powered ion pumping in a polystyrene sulfonate anion (PSS) doped polypyrrole (PPy) conducting polymer membrane (PSS-PPy) with a symmetric geometry. This PSS-PPy conducting polymer membrane exhibits a cationic selectivity and a light-responsive surface-charge-governed ion transport attributed to the negatively charged PSS groups. An asymmetric visible irradiation on one side of the PSS-PPy membrane induces a built-in electric field across the membrane due to the intrinsic photoelectronic property of PPy, which drives the cationic transport against the concentration gradient, demonstrating an ion-pumping effect. This work is a prototype that uses a geometry-symmetric conducting polymer membrane as a light-powered artificial ion pump for active ion transport, which exhibits potential applications in nanofluidic energy conversion.

Heterogeneous Charged Complexes of Random Copolymers for the Segregation of Organic Molecules.

Nature harnesses the disorder of intrinsically disordered proteins to organize enzymes and biopolymers into membraneless organelles. The heterogeneous nature of synthetic random copolymers with charged, polar, and hydrophobic groups has been exploited to mimic intrinsically disordered proteins, forming complexes with enzymatically active proteins and delivering them into nonbiological environments. Here, the properties of polyelectrolyte complexes composed of two random copolymer polyelectrolytes are studied experimentally and via simulation with the aim of exploiting such complexes for segregating organic molecules from water. The anionic polyelectrolyte contains hydrophilic and hydrophobic side chains and forms self-assembled hydrophobic domains. The cationic polymer is a high-molecular-weight copolymer of hydrophilic and charged side groups and acts as a flocculant. We find that the polyelectrolyte complexes obtained with this anionic and cationic random copolymer system are capable of absorbing small cationic, anionic, and hydrophobic organic molecules, including perfluorooctanoic acid, a compound of great environmental and toxicologic concern. Importantly, these macroscopic complexes can be easily removed from water, thereby providing a simple approach for organic contaminant removal in aqueous media. MARTINI and coarse-grained molecular dynamics simulations explore how the microscale heterogeneity of these random copolymer complexes relates to their segregation functionality.

Selection of a self-cleaving ribozyme activated in a chemically and thermally denaturing environment.

A new self-cleaving ribozyme was obtained from in vitro selection, displaying site-specific cleavage activity under denaturing conditions, such as high temperatures up to 95 °C, and denaturing solvents (20 M formamide). Adding salt such as Mg2+ also inhibited its activity. The conserved ribozyme sequence was found in the genome of several extremophiles, suggesting its potential biological relevance. This study provides an example of a ribozyme working under exotic conditions, which may expand the application of ribozymes in non-biological environments.

Insights into the Enhanced Catalytic Activity of Cytochrome c When Encapsulated in a Metal–Organic Framework

The encapsulation of enzymes within porous materials has shown great promise, not only in protecting the enzymes from denaturation under nonbiological environments, but also, in some cases, in facilitating their enzymatic reaction rates at favorable reaction conditions. While a number of hypotheses have been developed to explain this phenomenon, the detailed structural changes of the enzymes upon encapsulation within the porous material, which are closely related to their activity, remain largely elusive. Herein, the structural change of cytochrome c (Cyt c) upon encapsulation within a hierarchical metal-organic framework, NU-1000, is investigated through a combination of experimental and computational methods, such as electron paramagnetic resonance, solid-state ultraviolet-visible spectroscopy, and all-atom explicit solvent molecular dynamics simulations. The enhanced catalytic performance of Cyt c after being encapsulated within NU-1000 is supported by the physical and in silico observations of a change around the heme ferric active center.

Multiphoton Microscopy of Nonfluorescent Nanoparticles In Vitro and In Vivo.

Nanotechnology holds great promise for a plethora of potential applications. The interaction of engineered nanomaterials with living cells, tissues, and organisms is, however, only partly understood. Microscopic investigations of nano-bio interactions are mostly performed with a few model nanoparticles (NPs) which are easy to visualize, such as fluorescent quantum dots. Here the possibility to visualize nonfluorescent NPs with multiphoton excitation is investigated. Signals from silver (Ag), titanium dioxide (TiO2 ), and silica (SiO2 ) NPs in nonbiological environments are characterized to determine signal dependency on excitation wavelength and intensity as well as their signal stability over time. Ag NPs generate plasmon-induced luminescence decaying over time. TiO2 NPs induce photoluminescent signals of variable intensities and in addition strong third harmonic generation (THG). Optimal settings for microscopic detection are determined and then applied for visualization of these two particle types in living cells, in murine muscle tissue, and in the murine blood stream. Silica NPs produce a THG signal, but in living cells it cannot be discriminated sufficiently from endogenous cellular structures. It is concluded that multiphoton excitation is a viable option for studies of nano-bio interactions not only for fluorescent but also for some types of nonfluorescent NPs.

Synthesis and Self-Assembly of Bundle-Forming α-Helical Peptide-Dendron Hybrids.

Dendronized helix bundle assemblies combine the sequence diversity and folding properties of proteins with the tailored physical properties of dendrimers. Assembly of peptide-dendron hybrids into α-helical bundles encapsulates the helix bundle motif in a dendritic sheath that will allow the functional, protein-like domain to be transplanted to nonbiological environments. A bioorthogonal graft-to synthetic strategy for preparing helix bundle-forming peptide-dendron hybrids is described herein for hybrids 1a, 1b, and 2. Titration experiments monitored by circular dichroism spectroscopy support our self-assembly model for how the peptide-dendron hybrids self-assemble into α-helical bundles with the dendrons on outside of the bundle.

A Precision Scanning Probe Microscope with Direct Access to the Three Dimensional Tip-Sample Interaction Force Vector

Single-molecule imaging and force spectroscopy studies have produced rich insights into macromolecular structure and dynamics in biological settings and the atomic force microscope (AFM) has thus emerged as an important complementary apparatus in the structural biologist's toolkit. While conventional AFM has achieved sub-nm resolution imaging of membrane proteins in native membrane, atomic-scale tip-sample stability - which opens promising new avenues of AFM study - has previously only been achieved in highly isolated non-biological environments (i.e., cryogenic temperatures, ultra-high vacuum). We adapted techniques originally developed by the optical trapping microscopy community, and have constructed an ultra-stable AFM in which the tip and the sample positions are independently measured by, and stabilized with respect to, a pair of laser foci in three dimensions. Recently, we have extended ultra-stable AFM to common biological imaging conditions (tapping mode in aqueous buffer solution) and have exploited local observation of the three dimensional (3D) tip trajectories to yield 3D interaction force components in a direct manner. In this talk I will discuss these developments in the context of addressing central questions in membrane biophysics.

Synthesis of Single-Molecule Nanocars

The drive to miniaturize devices has led to a variety of molecular machines inspired by macroscopic counterparts such as molecular motors, switches, shuttles, turnstiles, barrows, elevators, and nanovehicles. Such nanomachines are designed for controlled mechanical motion and the transport of nanocargo. As researchers miniaturize devices, they can consider two complementary approaches: (1) the "top-down" approach, which reduces the size of macroscopic objects to reach an equivalent microscopic entity using photolithography and related techniques and (2) the "bottom-up" approach, which builds functional microscopic or nanoscopic entities from molecular building blocks. The top-down approach, extensively used by the semiconductor industry, is nearing its scaling limits. On the other hand, the bottom-up approach takes advantage of the self-assembly of smaller molecules into larger networks by exploiting typically weak molecular interactions. But self-assembly alone will not permit complex assembly. Using nanomachines, we hope to eventually consider complex, enzyme-like directed assembly. With that ultimate goal, we are currently exploring the control of nanomachines that would provide a basis for the future bottom-up construction of complex systems. This Account describes the synthesis of a class of molecular machines that resemble macroscopic vehicles. We designed these so-called nanocars for study at the single-molecule level by scanning probe microscopy (SPM). The vehicles have a chassis connected to wheel-terminated axles and convert energy inputs such as heat, electric fields, or light into controlled motion on a surface, ultimately leading to transport of nanocargo. At first, we used C(60) fullerenes as wheels, which allowed the demonstration of a directional rolling mechanism of a nanocar on a gold surface by STM. However, because of the low solubility of the fullerene nanocars and the incompatibility of fullerenes with photochemical processes, we developed new p-carborane- and ruthenium-based wheels with greater solubility in organic solvents. Although fullerene wheels must be attached in the final synthetic step, p-carborane- and ruthenium-based wheels do not inhibit organometallic coupling reactions, which allows a more convergent synthesis of molecular machines. We also prepared functional nanotrucks for the transport of atoms and molecules, as well as self-assembling nanocars and nanotrains. Although engineering challenges such as movement over long distance and non-atomically flat surfaces remain, the greatest current research challenge is imaging. The detailed study of nanocars requires complementary single molecule imaging techniques such as STM, AFM, TEM, or single-molecule fluorescence microscopy. Further developments in engineering and synthesis could lead to enzyme-like manipulation and assembly of atoms and small molecules in nonbiological environments.

Electrospun PCL in Vitro: a Microstructural Basis for Mechanical Property Changes

Polymeric tissue-engineering scaffolds must provide mechanical support while host-appropriate cells populate the structure and deposit extracellular matrix (ECM) components specific to the organ targeted for replacement. Even though this concept is widely shared, changes in polymer modulus and other mechanical properties versus biological exposure are largely unknown. This work shows that specific interactions of biological milieu with electrospun scaffolds can exert control over scaffold modulus. The net effects of biological and non-biological environments on electrospun structures following 7 and 28 days of in vitro exposure are established. Reduction of modulus, ultimate tensile strength and elongation occurs without the apparent involvement of classic hydrolysis mechanisms. We describe this phenomenon as deposition-induced inhibition of nanofiber rearrangement. This phenomenon shows that both mechanical and morphological characterization of electrospun structure under load in biological environments is required to tailor scaffold design to pursue specific tissue-engineering goals.

New design of helix bundle peptide-polymer conjugates.

We present a new design of peptide-polymer conjugates where a polymer chain is covalently linked to the side chain of a helix bundle-forming peptide. The effect of conjugated polymer chains on the peptide structure was examined using a de novo designed three-helix bundle and a photoactive four-helix bundle. Upon attachment of poly(ethylene glycol) to the exterior of the coiled-coil helix bundle, the peptide secondary structure was stabilized and the tertiary structure, that is, the coiled-coil helix bundle, was retained. When a heme-binding peptide as an example is used, the new peptide-polymer conjugate architecture also preserves the built-in functionalities within the interior of the helix bundle. It is expected that the conjugated polymer chains act to mediate the interactions between the helix bundle and its external environment. Thus, this new peptide-polymer conjugate design strategy may open new avenues to macroscopically assemble the helix bundles and may enable them to function in nonbiological environments.

From the Editor: All Things Bio

Corrosion has been classically associated with metallic objects in non-biological environments. But this is certainly no longer true—the corroding surfaces being studied have progressively encompassed other types of materials (e.g., polymers, semiconductors) over the years and the relevance of biological environments in corrosion processes has been increasingly recognized.

Survival of Influenza Virus on Banknotes

Successful control of a viral disease requires knowledge of the different vectors that could promote its transmission among hosts. We assessed the survival of human influenza viruses on banknotes given that billions of these notes are exchanged daily worldwide. Banknotes were experimentally contaminated with representative influenza virus subtypes at various concentrations, and survival was tested after different time periods. Influenza A viruses tested by cell culture survived up to 3 days when they were inoculated at high concentrations. The same inoculum in the presence of respiratory mucus showed a striking increase in survival time (up to 17 days). Similarly, B/Hong Kong/335/2001 virus was still infectious after 1 day when it was mixed with respiratory mucus. When nasopharyngeal secretions of naturally infected children were used, influenza virus survived for at least 48 h in one-third of the cases. The unexpected stability of influenza virus in this nonbiological environment suggests that unusual environmental contamination should be considered in the setting of pandemic preparedness.

Optimised Coverage of Non-self with Evolved Lymphocytes in an Artificial Immune System

The natural immune system (NIS) protects the body against unwanted foreign material (non-self cells) that could damage the body (self cells). The NIS can be modeled into an artificial immune system (AIS) to detect any non-self patterns in a non-biological environment. Detectors in the NIS can change from their initial mature status to memory status detectors or to annihilated status. A memory detector is a detector that fre- quently detects non-self cells and is a general detector for a sub- set of non-self cells. The NIS uses these memory detectors in a faster response to non-self cells. The purpose of this paper is to present the genetic artificial immune system (GAIS) which evolves these non-self detectors and determine their state using a life counter function. Only detectors with mature or memory status are used to detect non-self. Thus, the number of detectors is dynamically determined by the life counter function. In the paper GAIS is applied to different classification problems.

The evolution of eyes.

Eyes are the preeminent source of sensory information for the brain in most species, and many features of eyes reflect evolutionary solutions to particular selective pressures, both from the nonbiological environment and from other animals. As a result, the evolution of eyes, among all the sense organs, has attracted considerable attention from scientists. Paired eyes in the three major phyla, vertebrates, arthropods and mollusks, have long been considered to be classic examples of evolutionary convergence. At the macroscopic level, this must be true since they arise from different tissues and have evolved radically different solutions to the common problem of collecting and focusing light. However, opsin, the light-absorbing receptor protein, has a significant amount of shared DNA sequence homology across the phyla, and recently it has been discovered that some part of ocular development in different phyla is coordinated by a homologous, gene, Pax-6. So, although eyes from diverse phyla are clearly not homologous, neither can they be viewed as resulting solely from convergence. Instead, this shows that homology at the molecular level of organization does not predict homology at the organ or organismic level. The presence of homologous constituent molecules in nonhomologous structures reminds us that molecules are not eyes.

Canonical correlations of seed viability, seed-borne fungi, and environment in bulk grain ecosystems

Canonical correlation analyses were performed to determine relationships among seed-viability, fungi, and environment in two bulk grain ecosystems. Measurements of 20 variables were made on 8135 samples from two wheat bulks in a farm granary in Winnipeg during 1959–1967. The canonical vectors were interpreted by correlating each set of two canonical variates with the original variates on which they were based. The highest and the second highest significant (P < 0.001) canonical correlation for each combination were field fungi and germination vs. non-biological environment, 0.91 and 0.32; storage fungi vs. non-biological environment, 0.77 and 0.42; field fungi and germination vs. storage fungi, 0.78 and 0.35. In aging grain bulks the attack of the storage fungi Chaetomium funicolum, Streptomyces griseus, Aspergillus spp., and Rhizopus arrhizus involves the loss of grain viability and decrease in the field fungi, Alternaria tenuis, Cochliobolus sativus, and Gonatobotrys simplex. Collectively grain temperature and the granary conditions are most important in the reduction of the field fungi; whereas temperature, moisture content, and time are most involved in the infestation of S. griseus, Penicillium spp., C. funicolum, Aspergillus spp., and R. arrhizus.