Archive for the ‘Hot Articles’ Category

It’s getting tense: researchers find new evidence about the nature of cell spreading

Graphical abstract

Cell spreading increases with increasing tension tolerance

What are the mechanisms behind cell spreading? Chowdhury et al. decided to apply a multidisciplinary approach to this biophysical mystery.

Described in the last blog post on breast cancer mechanics, it’s clear that the extracellular matrix (ECM) is a dynamic and supportive microenvironment for cell. Cell specialisation includes flattening onto the ECM, and this is an important morphological step in determining the future of the cell’s proliferation and differentiation. If the process malfunctions, this could be the difference between life and death for the cell. The sensing mechanism behind the cell spreading and the importance of molecular tethering in the process, however, is not so clear. The researchers hypothesised that molecular tension drives cell spreading rather than molecular stiffness, a claim that has been difficult to validate because of the difficulty in decoupling these two phenomena.

Two of the researchers developed a method for defining the single molecular forces between the cell and the ECM, called the tension gauge tether. A tether such as DNA is attached to a ligand, which will join to a receptor within the cell membrane. If tension is too high, the tether will snap. This allowed the researchers to design TGTs with different tension tolerances and measure the consequential amount of cell spreading. Integrins are receptors that join the ECM outside a cell to the cytoskeleton inside the cell, and so were good candidates for measuring tension.

It was found that cell area increases in line with higher tension tolerances, and a similar amount of cell spreading was found across multiple different molecular stiffness surfaces.  This finding suggests that molecular stiffness has little influence over cell spreading, while molecular tension is key.


You can read the full paper for free* using the link below:

Single molecular force across single integrins dictates cell spreading
F. Chowdhury, I.T.S. Li, B.J. L. Doğanay, R. Singh, X. Wang, J. Seong, S. Lee, S. Park, N. Wang, T. Ha
Integr. Biol., 2015, Advance Article
DOI: 10.1039/C5IB00080G, Paper

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About the webwriter

Rebecca Muir is a research assistant in the Medical Sciences Division of Oxford University. Her research interests include cell biology, gender studies, philosophy of science, and mitochondrial disease. Rebecca was shortlisted for the Chemistry World’s Science Communication Competition 2015. She tweets at @rebeccalydiam and her personal website can be found on rebeccamuir.co.uk.

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*Access is free until 17/09/2015 through a registered RSC account.

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The dynamics of breast cancer mechanics

According to Cancer Research UK, Breast Cancer in the third commonest type of cancer diagnosed and accounts for 15% of all female cancer deaths. A clear understanding of the biology behind this malignancy is urgently needed. With that in mind, researchers at the University of California San Francisco have unravelled the specific invasive properties of breast cancer tumours.

Acerbi et al. investigated the link between breast cancer tissue and the stiffness of the tissue scaffold, the extracellular matrix (ECM). In non-cancerous tissues, the ECM is integral for the maintenance of tissue structure and is a regulator of the dynamic communication between cells. Characteristically, the ECM is collagen-rich yet can take many forms depending on the need of the tissue because of its responsive nature. This active role of the ECM unfortunately presents the opportunity for deleterious remodelling. The researchers found that hallmarks of the tumour transformation include deposition of excessive collagen, elevated mechanosignalling and an association with a stiffened ECM at the invasive front of the tumour.

Compared to normal breast tissue, the collagen was progressively assembled into thicker fibres and linearised, causing stiffening of the ECM. Macrophages sent by the immune system release soluble factors that assist with the remodelling. The researchers correlated the influx of immune cells with the increase in SMAD signalling, a cascade which changes the gene expression of the tissue and is likely to be part of the molecular pathway behind the extra collagen production.

The core tissue of the tumour was less stiff than the invasive edge

The researchers identified that tumours caused by different breast cancer-associated mutations can have diverse ECM compositions, and even different regions of the same tumour can be biochemically distinct. This has important implications for the testing and imaging of breast cancer tumours and provides convincing evidence that the ECM is more complex in cancer pathology than previously thought.


You can read the full paper for free* using the link below:
Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration
I. Acerbi, L. Cassereau, I. Dean, Q. Shi, A. Au, C. Park, Y. Y. Chen, J. Liphardt, E. S. Hwang and V. M. Weaver
Integr. Biol., 2015, Advance Article
DOI: 10.1039/C5IB00040H, Paper

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About the webwriter

Rebecca Muir is a research assistant in the Medical Sciences Division of Oxford University. Her research interests include cell biology, gender studies, philosophy of science, and mitochondrial disease. Rebecca was shortlisted for the Chemistry World’s Science Communication Competition 2015. She tweets at @rebeccalydiam and her personal website can be found on rebeccamuir.co.uk.

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*Access is free until 16/08/2015  through a registered RSC account.

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May’s HOT Article

Article of the month for May, recommended by our referees, is free* to access for a limited time only!


Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration

I. Acerbi, L. Cassereau, I. Dean, Q. Shi, A. Au, C. Park, Y. Y. Chen, J. Liphardt, E. S. Hwang and V. M. Weaver
Integr. Biol., 2015, Advance Article
DOI: 10.1039/C5IB00040H

This article was part of our Mechanobiology themed collection!

*Access is free until 24.07.2015 through a publishing personal account. It’s quick, easy and free to register!

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Implications in diabetes explored with a 3D-printed fluidic device

Type 1 Diabetes has confused doctors for centuries. Characterised by the auto-immune destruction of pancreatic beta cells, sudden and debilitating symptoms can arise without insulin treatment. Insulin is only one amongst three known hormones produced by the beta cell, leading researchers at Michigan State University (MSU) to examine one of these mysterious molecules, called C-peptide.

The life expectancy of a person with type-1 diabetes has increased significantly compared to pre-20th century, but unfortunately chronic complications still may develop, such as heart disease, nerve damage and retinopathy. However, there is evidence that short-term replacement of C-peptide could improve the progression of the disease, by enhancing the ability of red blood cells to affect blood flow. Using a 3D-printed fluidic device, Researchers at MSU tested the hypothesis that C-peptide combined with a charged form of zinc (Zn2+) would cause blood vessel dilation, by increasing the amounts of ATP, an energy-carrier molecule shown to stimulate the vessel dilator nitric oxide (NO).

The 3D-printed fluidic device provides an experimental model for investigating cellular communication in the pancreas. Red blood cells flowed in the albumin-containing buffer under INS-1 cells and ATP release was measured.

This platform allowed the researchers to examine the tissue-tissue communication between rat INS-1 cells (which can serve as a beta-cell mimic) and a blood vessel-like endothelium, a currently impossible task to achieve in vivo.

Initially it was thought that Zn2+ facilitated delivery of C-peptide to the red blood cells, but it was soon found the delivery was actually enhanced by Albumin, a peptide carrier in the bloodstream.

However, red blood cells incubated with C-peptide alone did not show a significant ATP increase – they found it is in fact a joint effort, where both zinc and C-peptide are delivered by albumin to the endothelium. This suggests that the next steps are to test zinc, C-peptide and albumin combinational treatment alongside insulin, and to identify the C-peptide receptor itself.

The full article is free to access until 3 July 2015 and can be found on the link below:

C-peptide and zinc delivery to erythrocytes requires the presence of albumin: implications in diabetes explored with a 3D-printed fluidic device

Yueli Liu, Chengpeng Chen, Suzanne Summers, Wathsala Medawala and Dana M. Spence

Integr. Biol., 2015,7, 534-543
DOI: 10.1039/C4IB00243A
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April’s HOT Article

Article of the month for April, recommended by our referees, is free* to access for a limited time only!

Two macrocyclic polyamines as modulators of metal-mediated Aβ40 aggregation
Yanfei Yang, Tingting Chen, Shajun Zhu, Xuefang Gu, Xueping Jia, Yapeng Lub and Li Zhu
Integr. Biol., 2015, Advance Article
DOI: 10.1039/C5IB00064E, Paper

Take a look at our Integrative Biology 2014 HOT Articles Collection!

*Access is free until 29.06.2015 through a publishing personal account. It’s quick, easy and free to register!

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March’s HOT Article

Article of the month for March, recommended by our referees, is free* to access for a limited time only!

Analysis of sphingosine kinase activity in single natural killer cells from peripheral blood

Alexandra J. Dickinson, Megan Meyer, Erica A. Pawlak, Shawn Gomez, Ilona Jaspers and Nancy L. Allbritton

Integr. Biol., 2015, 7, 392-401
DOI: 10.1039/C5IB00007F, Paper

Take a look at our Integrative Biology 2014 HOT Articles Collection!

*Access is free until 31.05.2015 through a publishing personal account. It’s quick, easy and free to register!

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Capillary electrophoresis to analyse enzymatic pathways in natural killer cells

Natural killer (NK) cells are a type of lymphocyte that are vitally important in the body’s immune response. These cells show high levels of heterogeneity, with an estimated 6000 to 30000 distinct subsets in the circulating blood of just one person. Because of this, technologies are needed that are capable of measuring single cells.

Allbritton and co-workers, at the University of North Carolina, have reported a method for doing just this using an automated single-cell capillary electrophoresis (CE) system. This system works by capturing individual NK cells in cell traps (consisting of 15µm diameter microwells) and positioning a capillary above one of the cell traps. The cell is lysed using a laser pulse and the cellular contents are injected into the capillary electrokinetically. The capillary is programmed to transfer the cellular contents to the electrophoretic buffer, where separation occurs. The capillary then moves back to the next cell trap and repeats the process.

The work in this paper focuses on the spingosine-1-phosphate (S1P) pathway (shown in the diagram below), which is important in the regulation of lymphocyte migration and differentiation, and cytokine production. Fluorescently labelled sphingosine was loaded into the NK cells of healthy human subjects and, following incubation, the cells were loaded onto the microwells and analysed using the single-cell CE system. The amount of each metabolite present was then identified from the electropherogram. The authors identified three major peaks, corresponding to fluorescently labelled sphingosine, S1P and hexadecanoic acid.  From the relative amounts of each metabolite, the activity of various enzymes in the S1P pathway were assessed.

The activity within the S1P pathway was found to be highly heterogeneous in NK cells obtained from one individual, as well as those from different subjects. In the majority of cells, phosphorylation of sphingosine was upregulated relative to the breakdown of S1P. No peaks were seen that corresponded to the ceramide metabolite, suggesting that in healthy humans, sphingosine is metabolised to S1P more rapidly.

By increasing the throughput of the automated system and preparing additional fluorescent reporters, this automated CE system has the potential to provide a more comprehensive picture of an individual cell’s signalling pathways.



To download the full article for free* click the link below:
Analysis of sphingosine kinase activity in single natural killer cells from peripheral blood
Alexandra J. DickinsonMegan MeyerErica A. PawlakShawn GomezIlona Jaspers and Nancy L. Allbritton
DOI: 10.1039/C5IB00007F


*Access is free until 31.05.2014 through a registered publishing personal account

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January’s HOT Article

Article of the month for January, recommended by our referees, is free* to access for a limited time only!

Graphical Abstract

Magnetic engineering of stable rod-shaped stem cell aggregates: circumventing the pitfall of self-bending
V. Du, D. Fayol, M. Reffay, N. Luciani, J-C. Bacri, C. Gay and C. Wilhelm
Integr. Biol., 2015,7, 170-177
DOI: 10.1039/C4IB00219A

Take a look at our Integrative Biology 2015 HOT Articles Collection!

 

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How are neurons like social networks?

News travels fast on Facebook. You post a YouTube video, and by the next day, your cousin’s roommate’s friend’s ex-boyfriend in Australia is watching it.

Facebook is a prime example of what is known as a small-world network. Each node (in this case, a person) is only connected to a few others within the network (their “friends”), but because the way that interconnected nodes cluster together, no node is more than a few steps away from any other. It’s a virtual demonstration of the classic six degrees of separation paradigm.

Now, scientists are investigating whether neural networks use similar strategies to efficiently transmit complex information. For example, in a recent study published in the Royal Society of Chemistry journal Integrative Biology, an international team of researchers examined how the nanostructure of silicon surfaces affected the way neural networks formed on it.

The team grew neuroblastoma brain cancer cells on two different silicon substrates: one smooth, the other etched with nanoscale pores. (Neuroblastoma cells display many of the same properties as ordinary neurons but are easier to grow in culture.)  The cells grew much more quickly on the etched silicon than on the smooth surface. Furthermore, the porous, etched silicon induced the cells to form a more clustered network with a small-world topology. It appeared that the nanoscale-level constraints induced the cells to form more efficient network structures.

Porous silicon has shown promise in biomedical applications. These results suggest that biomedical engineers could influence the way neural networks form on silicon by modifying its surface. And while it has not been experimentally demonstrated, the researchers suggest that similar nanoscale cues within the brain could influence the formation of neural networks in the human brain and guide them towards more efficient configurations.

The full paper by Marinaro et al is free* to access until 9th March 2015. Download now by clicking the link below:

Networks of neuroblastoma cells on porous silicon substrates reveal a small world topology

* Access is free through a registered RSC account – click here to register

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December’s HOT Article

Article of the month for December, recommended by our referees, is free* to access for a limited time only!

 Graphical Abstract

 A biologically inspired lung-on-a-chip device for the study of protein-induced lung inflammation
Tushar H. Punde,  Wen-Hao Wu, Pei-Chun Lien,  Ya-Ling Chang, Ping-Hsueh Kuo,  Margaret Dah-Tsyr Chang, Kang-Yun Lee, Chien-Da Huang, Han-Pin Kuo, Yao-Fei Chan, Po-Chen Shih and  Cheng-Hsien Liu
Integr. Biol., 2015, Advance Article
DOI: 10.1039/C4IB00239C 

Take a look at our Integrative Biology 2014 HOT Articles Collection!

 

*Access is free through a publishing personal account. It’s quick, easy and free to register!

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