20 research outputs found
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Electrostatic Localization of RNA to Protocell Membranes by Cationic Hydrophobic Peptides
Cooperative interactions between RNA and vesicle membranes on the prebiotic earth may have led to the emergence of primitive cells. The membrane surface offers a potential platform for the catalysis of reactions involving RNA, but this scenario relies upon the existence of a simple mechanism by which RNA could become associated with protocell membranes. Here, we show that electrostatic interactions provided by short, basic, amphipathic peptides can be harnessed to drive RNA binding to both zwitterionic phospholipid and anionic fatty acid membranes. We show that the association of cationic molecules with phospholipid vesicles can enhance the local positive charge on a membrane and attract RNA polynucleotides. This phenomenon can be reproduced with amphipathic peptides as short as three amino acids. Finally, we show that peptides can cross bilayer membranes to localize encapsulated RNA. This mechanism of polynucleotide confinement could have been important for primitive cellular evolution
Bipolar resistive switching and memristive properties of hydrothermally synthesized TiO2 nanorod array: Effect of growth temperature
The final publication is available at Elsevier via https://dx.doi.org/10.1016/j.matdes.2018.04.046 © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/In the present work, the hydrothermal approach is employed to develop 1D-TiO2 nanorod array memristive devices and the effect of hydrothermal growth temperature on TiO2 memristive devices is studied. X-ray diffraction (XRD) analysis suggested that the rutile phase is dominant in the developed TiO2 nanorod array. Field emission scanning electron microscopy (FESEM) images show well adherent and pinhole free one dimensional (1D) TiO2 nanorods. The presence of titanium and oxygen in all the samples was confirmed by energy dispersive X-ray spectroscopy (EDS). Furthermore, growth of the 1D TiO2 nanorods depends on the growth temperature and uniform growth is observed at the higher growth temperatures. The well-known memristive hysteresis loop is observed in the TiO2 nanorod thin films. Furthermore, resistive switching voltages, the shape of I-V loops and (non)rectifying behavior changed as the growth temperature varied from 140 °C to 170 °C. The biological synapse properties such as paired-pulse facilitation and short-term depression are observed in some devices. The detailed electrical characterizations suggested that the developed devices show doubled valued charge-magnetic flux characteristic and charge transportation is due to the Ohmic and space charge limited current.Funding from School of Nanoscience and Biotechnology, Shivaji University, Kolhapu
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Deconstructing synthetic biology across scales: A conceptual approach for training synthetic biologists
Synthetic biology allows us to reuse, repurpose, and reconfigure biological systems to address society’s most pressing challenges. Developing biotechnologies in this way requires integrating concepts across disciplines, posing challenges to educating students with diverse expertise. We created a framework for synthetic biology training that deconstructs biotechnologies across scales—molecular, circuit/network, cell/cell-free systems, biological communities, and societal—giving students a holistic toolkit to integrate cross-disciplinary concepts towards responsible innovation of successful biotechnologies. We present this framework, lessons learned, and inclusive teaching materials to allow its adaption to train the next generation of synthetic biologists
Finishing the euchromatic sequence of the human genome
The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
Tuning Targeted Liposome Avidity to Cells via Lipid Phase Separation
The addition of both cell-targeting moieties and polyethylene
glycol
(PEG) to nanoparticle (NP) drug delivery systems is a standard approach
to improve the biodistribution, specificity, and uptake of therapeutic
cargo. The spatial presentation of these molecules affects avidity
of the NP to target cells in part through an interplay between the
local ligand concentration and the steric hindrance imposed by PEG
molecules. Here, we show that lipid phase separation in nanoparticles
can modulate liposome avidity by changing the proximity of PEG and
targeting protein molecules on a nanoparticle surface. Using lipid-anchored
nickel-nitrilotriacetic acid (Ni-NTA) as a model ligand, we demonstrate
that the attachment of lipid anchored Ni-NTA and PEG molecules to
distinct lipid domains in nanoparticles can enhance liposome binding
to cancer cells by increasing ligand clustering and reducing steric
hindrance. We then use this technique to enhance the binding of RGD-modified
liposomes, which can bind to integrins overexpressed on many cancer
cells. These results demonstrate the potential of lipid phase separation
to modulate the spatial presentation of targeting and shielding molecules
on lipid nanocarriers, offering a powerful tool to enhance the efficacy
of NP drug delivery systems
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Oligoarginine Peptides Slow Strand Annealing and Assist Nonenzymatic RNA Replication
The nonenzymatic replication of RNA is thought to have been a critical process required for the origin of life. One unsolved difficulty with nonenzymatic RNA replication is that template-directed copying of RNA results in a double-stranded product; following strand separation, rapid strand reannealing outcompetes slow nonenzymatic template copying, rendering multiple rounds of RNA replication impossible. Here we show that oligoarginine peptides slow the annealing of complementary oligoribonucleotides by up to several thousand-fold; however, short primers and activated monomers can still bind to template strands, and template-directed primer extension can still occur within a phase-separated condensed state, or coacervate. Furthermore, we show that within this phase, partial template copying occurs even in the presence of full-length complementary strands. This method for enabling further rounds of replication suggests one mechanism by which short, non-coded peptides could have enhanced early cellular fitness, potentially explaining how longer, coded peptides, i.e. proteins, came to prominence in modern biology
Correction: Retraction: Oligoarginine peptides slow strand annealing and assist non-enzymatic RNA replication
Diblock copolymers enhance folding of a mechanosensitive membrane protein during cell-free expression
Copying of Mixed-Sequence RNA Templates inside Model Protocells
The chemical replication
of RNA inside fatty acid vesicles is a
plausible step in the emergence of cellular life. On the primitive
Earth, simple protocells with the ability to import nucleotides and
short oligomers from their environment could potentially have replicated
and retained larger genomic RNA oligonucleotides within a spatially
defined compartment. We have previously shown that short 5′-phosphoroimidazolide-activated
“helper” RNA oligomers enable the nonenzymatic copying
of mixed-sequence templates in solution, using 5′-phosphoroimidazolide-activated
mononucleotides. Here, we report that citrate-chelated Mg<sup>2+</sup>, a catalyst of nonenzymatic primer extension, enhances fatty acid
membrane permeability to such short RNA oligomers up to the size of
tetramers, without disrupting vesicle membranes. In addition, selective
permeability of short, but not long, oligomers can be further enhanced
by elevating the temperature. The ability to increase the permeability
of fatty acid membranes to short oligonucleotides allows for the nonenzymatic
copying of RNA templates containing all four nucleotides inside vesicles,
bringing us one step closer to the goal of building a protocell capable
of Darwinian evolution