DNA cages 'can survive inside living cells'

DNA cages 'can survive inside living cells'

  5:07:00 PM    Science Lover

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Scientists at Oxford University have shown for the first time that molecular cages made from DNA can enter and survive inside living cells.

Human embryonic kidney cells were used to test the DNA cages

The work, a collaboration between physicists and molecular neuroscientists at Oxford, shows that artificial DNA cages that could be used to carry cargoes of drugs can enter living cells, potentially leading to new methods of drug delivery.

A report of the research is published online in the journal ACS Nano.

The cages developed by the researchers are made from four short strands of synthetic DNA. These strands are designed so that they naturally assemble themselves into a tetrahedron (a pyramid with four triangular faces) around 7 nanometres tall.

The Oxford researchers have previously shown that it is possible to assemble these cages around protein molecules, so that the protein is trapped inside, and that DNA cages can be programmed to open when they encounter specific ‘trigger’ molecules that are found inside cells.



In the new experiment they introduced fluorescently-labelled DNA tetrahedrons into human kidney cells grown in the laboratory. They then examined the cells under the microscope and found that the cages remained substantially intact, surviving attack by cellular enzymes, for at least 48 hours. This is a crucial advance: to be useful as a drug delivery vehicle, a DNA cage must enter cells efficiently and survive until it can release its cargo where and when it is needed.

‘At the moment we are only testing our ability to create and control cages made of DNA,’ said Professor Andrew Turberfield of Oxford University’s Department of Physics, who led the work. ‘However, these results are an important first step towards proving that DNA cages could be used to deliver cargoes, such as drugs, inside living cells.’

Professor Turberfield said: ‘Previous studies have shown that the size of particles is an important factor in whether or not they can easily enter cells, with particles with a radius less than 50 nanometres proving much more successful at gaining entry than larger particles. At 7 nanometres across our DNA tetrahedrons are compact enough to easily enter cells but still large enough to carry a useful cargo. More work is now needed to understand exactly how these DNA cages manage to find their way inside living cells.’
Provided by Oxford University

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Depression Drugs-SSRIs-May Reorganize Brain Plasticity, New Research Suggests

Depression Drugs-SSRIs-May Reorganize Brain Plasticity, New Research Suggests

  9:19:00 AM    Science Lover

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Selective serotonin reuptake inhibitors (SSRI) such as Prozac are regularly used to treat severe anxiety and depression. They work by immediately increasing the amount of serotonin in the brain and by causing long term changes in brain function. However it can take weeks of treatment before a patient feels any effect and both beneficial effects and side effects can persist after treatment is stopped.

New research investigates physiological changes within the brain that may be caused by selective serotonin reuptake inhibitors. (Credit: iStockphoto/Sebastian Kaulitzki)

New research published by BioMed Central's open access journal Molecular Brain investigates physiological changes within the brain that may be caused by SSRI treatment.

The hippocampus is an area of the brain involved in long term memory and spatial awareness, and is involved in symptoms afflicting people with Alzheimer's disease, such as loss of memory and disorientation. Neuronal cells in the hippocampus can change their activity and strength of connections throughout life, a process known as plasticity, which thought to be one of the ways new memories are formed. Altered plasticity is often associated with depression and stress.

Researchers from the Department of Pharmacology, Nippon Medical School, showed that chronic treatment of adult mice with fluoxetine (Prozac) caused changes to granule cells, one of the main types of neuronal cells inside the hippocampus, and to their connections with other neuronal cells. The granule cells appeared to undergo serotonin-dependent 'dematuration', which increased their activity and reversed adult-type plasticity into an immature state. These changes to the cell's plasticity were associated with increased anxiety and in alternating between periods of hyper or hypo activity.

Katsunori Kobayashi explained, "Some of the side effects associated with Prozac in humans, such as anxiety and behavioral switching patterns, may be due to excessive dematuration of granule cells in the hippocampus."

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Artificial Cells Behave Like Biological Cells

Artificial Cells Behave Like Biological Cells

  7:42:00 PM    Science Lover

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Inspired by the social interactions of ants and slime molds, University of Pittsburgh engineers have designed artificial cells capable of self-organizing into independent groups that can communicate and cooperate.

The above image shows the cells in “snake” formation 
as competing signaling capsules (shown in red) pull 
respective lines of target cells in opposite 
directions. (Credit: University of Pittsburgh)

Recently reported in the Proceedings of the National Academy of Sciences (PNAS), the research is a significant step toward producing synthetic cells that behave like natural organisms and could perform important, microscale functions in fields ranging from the chemical industry to medicine.

The team presents in the PNAS paper computational models that provide a blueprint for developing artificial cells -- or microcapsules -- that can communicate, move independently, and transport "cargo" such as chemicals needed for reactions. Most importantly, the "biologically inspired" devices function entirely through simple physical and chemical processes, behaving like complex natural organisms but without the complicated internal biochemistry, said corresponding author Anna Balazs, Distinguished Professor of Chemical Engineering in Pitt's Swanson School of Engineering.

The Pitt group's microcapsules interact by secreting nanoparticles in a way similar to that used by biological cells signal to communicate and assemble into groups. And with a nod to ants, the cells leave chemical trails as they travel, prompting fellow microcapsules to follow. Balazs worked with lead author German Kolmakov and Victor Yashin, both postdoctoral researchers in Pitt's Department of Chemical and Petroleum Engineering, who produced the cell models; and with Pitt professor of electrical and computer engineering Steven Levitan, who devised the ant-like trailing ability.

The researchers write that communication hinges on the interaction between microcapsules exchanging two different types of nanoparticles. The "signaling" cell secretes nanoparticles known as agonists that prompt the second "target" microcapsule to emit nanoparticles known as antagonists.

In one video of the interaction, as the signaling cell emits the agonist nanoparticles, the target cell responds with antagonists that stop the first cell from secreting. Once the signaling cell goes dormant, the target cell likewise stops releasing antagonists -- which makes the signaling cell start up again. The microcapsules get locked into a cycle that equates to an intercellular conversation, a dialogue humans could control by adjusting the capsules' permeability and the quantity of nanoparticles they contain.

Locomotion results as the released nanoparticles alter the surface underneath the microcapsules. The cell's polymer-based walls begin to push on the fluid surrounding the capsule and the fluid pushes back even harder, moving the capsule. At the same time, the nanoparticles from the signaling cell pull it toward the target cells. Groups of capsules begin to form as the signaling cell rolls along, picking up target cells. In practical use, Balazs said, the signaling cell could transport target cells loaded with cargo; the team's next step is to control the order in which target cells are collected and dropped off.

The researchers adjusted the particle output of the signaling cell to create various cell formations. One video clip shows the trailing "ants," wherein the particle secretions of one microcapsule group are delayed until another group passes by and activates it. The newly awakened cluster then follows the chemical residue left behind by the lead group.

A second film depicts a "dragon" formation comprising two cooperating signaling cells (shown as red) leading a large group of targets. Similar to these are "snakes" made up of competing signaling capsules pulling respective lines of target cells.

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