An official website of the United States government
Graphene is a valuable material in biomedical implant applications due to its mechanical integrity, long-range order, and conductivity; but graphene must be chemically modified to increase biocompatibility and maximize functionality in the body. Here, we developed a foundational synthetic method for covalently functionalizing a reduced GO with bioactive molecules, focusing on synthetic peptides that have shown osteogenic or neurogenic capability as a prototypical example. X-ray photoelectron spectroscopy provides evidence that the peptide is covalently linked to the graphenic backbone. These peptide–graphene (Pep–G) conjugate materials can be processed into mechanically robust, three-dimensional constructs. Differences in their electrostatic charges allow the Pep–G conjugates to form self-assembled, layer-by-layer coatings. Further, the Pep–G conjugates are cytocompatible and electrically conductive, leading us to investigate their potential as regenerative scaffolds, as conductive surfaces can stimulate bone and nerve regeneration. Notably, PC12 cells grown on an electrically stimulated Pep–G scaffold demonstrated enhanced adhesion and neurite outgrowth compared to the control. The functionalization strategy developed here can be used to conjugate a wide variety of bioactive molecules to graphene oxide to create cell-instructive surfaces for biomedical scaffold materials.
more »
« less
Light-Induced Metal-Free Transformations of Unactivated Pyridotriazoles
A highly efficient and practical method for incorporation of arylmethylpyridyl moiety into diverse molecules has been developed. This method features the transition metal-free light-induced room temperature transformation of pyridotriazoles into pyridyl carbenes, which are capable of smooth arylation, X–H insertion, and cyclopropanation reactions. The synthetic usefulness of the developed method was illustrated in a facile synthesis of biologically active molecules.
more »
« less
- Award ID(s):
- 1663779
- PAR ID:
- 10106880
- Date Published:
- Journal Name:
- Chemical Science
- ISSN:
- 2041-6520
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Mass spectrometry imaging is a powerful technique for mapping the spatial distribution of endogenous and exogenous molecules in biological tissues, but it is limited to relative quantitation. To address this limitation, we developed an integrated approach that combines desorption electrospray ionization mass spectrometry imaging with coulometric mass spectrometry to achieve the absolute quantification of drug molecules at the pixel level, without the use of external standards or isotopic labeling. We applied this method to quantify olanzapine, an antipsychotic drug, and its minor hepatic metabolite, 2-hydroxymethylolanzapine, in rat liver tissue. CMS enabled the electrochemical redox quantification of both compounds extracted from tissue regions of interest as defined by mass spectrometry imaging. This established a direct correlation between the imaging signal intensity and the absolute analyte concentration. Our results demonstrate the robustness and sensitivity of this combined approach and support its potential as a generalizable platform for standard-free, quantitative imaging of biological tissues, thereby converting relative ion maps into fully quantitative molecular images.more » « less
-
null (Ed.)Creating a suitable compartment for synthetic cells has led the exploration of different cell chassis materials from phospholipids to polymer to protein-polymer conjugates. Currently, the majority of cell-like compartments are made of lipid molecules as the resulting membrane resembles that of a natural cell. However, cell-sized lipid vesicles are prone to physical and chemical stresses and can be unstable in hosting biochemical reactions within. Recently, peptide vesicles that are more robust and stable were developed as a new chassis material for synthetic cells. Here we demonstrate the facile and robust generation of giant peptide vesicles made of elastin-like polypeptides (ELPs) by using an emulsion transfer method. We show that these peptide vesicles can stably encapsulate molecules and can host cell-free expression reactions. We also demonstrate membrane incorporation of another amphiphilic ELP into existing peptide vesicles. Since ELPs are genetically encoded, the approaches presented here provide exciting opportunities to engineer synthetic cell membranes.more » « less
-
null (Ed.)Cells often respond to changes in their environment by producing new molecules and building new cell components, such as proteins, which perform most tasks in the cell, or DNA and RNA, which carry genetic information. Complex tissues – such as limbs, which are made up of muscles, tendons, bones and cartilage – are difficult to see through, so studying when and where cells in these tissues produce different types of molecules is challenging. New approaches combining advanced three-dimensional microscopy and fluorescent labelling of molecules could provide a way to study these processes within whole animal tissues. One application for this is studying how salamanders regrow lost limbs. When salamanders such as axolotls regrow a limb, some cells in the limb stump form a group called the blastema. The blastema contains cells that are specialized to different purposes. Each cell in the blastema produces many new proteins as well as new DNA and RNA molecules. Fluorescently labeling particular molecules and taking images of the regenerating limb at different times can help to reveal how these new molecules control and coordinate limb regrowth. Duerr et al. developed a three-dimensional microscopy technique to study the production of new molecules in regenerating axolotl limbs. The method labeled molecules of different types with fluorescent markers. As a result, new proteins, RNA and DNA glowed under different colored lights. Duerr et al. used their method to show that nerve damage, which hinders limb regrowth in salamanders, reduces DNA production in the blastema. There are many possible applications of this microscopy method. Since the technique allows the spatial arrangement of the cells and molecules studied to be preserved, it makes it possible to investigate which molecules each cell is making and how they interact across a tissue. Not only does the technique have the potential to reveal much more about limb regrowth at all stages, but the fluorescent markers used can also be easily adapted to many other applications.more » « less
-
Building upon our previously developed time-dependent Hartree–Fock (TDHF)@vW method, based on many-body perturbation theory and, specifically, the Bethe–Salpeter Equation (BSE), we introduce a parameterization scheme for the attenuated exchange kernel, vW(|r − r′|). In the original method, vW was determined individually for each system via an efficient stochastic short-time TD Hartree propagation for the screened Coulomb interaction, W(r, r′). The new parameterization leverages photophysical similarities in exciton binding energies (or exchange interaction attenuation) among molecules with comparable static dielectric responses. We parameterize the inverse dielectric function using a low-order polynomial with error function apodization, calibrated on a few representative molecules, each with its own vW. Using only seven parameters, the parameterized vW is fully grid-independent and broadly applicable within a family of molecules. This enables TDHF@vW that retains BSE-level accuracy, achieving a mean absolute error of ∼0.1 eV compared to experimental optical gaps and representing a five- to tenfold improvement over conventional TD density functional theory or TDHF while reducing the cost to that of standard TDHF.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript
- Journal Article:
- https://doi.org/10.1039/C9SC02448D
