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Stress applied to cancerous and non-cancerous cells stuck to nanofibres causes the cancerous cells to become unfixed

US scientists have found a way to separate cancerous cells from healthy cells by taking advantage of their adhesion properties. Separating cancer cells for analysis is a critical step for determining the recommended course of treatment for patients.

See the full article in Chemistry World

Or read the Integrative Biology paper:

Plasma surface modification of electrospun fibers for adhesion-based cancer cell sorting
B. N. Blackstone, J. J. Willard, C. H. Lee, M. T. Nelson, R. T. Hart, J. J. Lannutti and H. M. Powell
DOI: 10.1039/C2IB20025B

Scientists in China have discovered that the blood plasma proteins of type II diabetes patients reduce the beneficial effects of dietary polyphenols.

Raised glucose levels in the blood of diabetics affects the structure of their blood plasma proteins, which prevents the proteins carrying healthy antioxidants to cells and tissues

Polyphenols are antioxidants and are found in chocolate and red wine, for example. In the body, they scavenge cell damaging free radicals. They bind to proteins in blood plasma, constantly switching between the bound and unbound forms. This may be how polyphenols are delivered to cells and tissues, but this is unproven.

Diabetics have raised levels of glucose in their blood. Glucose can also bind to plasma proteins, says Jianbo Xiao of Shanghai Normal University, who led the research. ‘Exposing plasma proteins to glucose influences their structures and functions,’ he says. So, to investigate this influence, Xiao’s team studied the polyphenol-binding abilities of healthy plasma proteins and compared them to the binding abilities of type II diabetes plasma proteins using fluorescence spectroscopy.

The team found that type II diabetes plasma proteins have an affinity 1 to 10 times lower for polyphenols than healthy proteins. ‘The non-covalent interactions between polyphenols and plasma proteins are usually caused by four major forces: hydrogen bonding, van der Waals forces, hydrophobic interactions and electrostatic interactions,’ says Xiao. The difference between the affinities was larger when more hydrophobic polyphenols were tested. There was only a slight difference in the affinity when the polyphenol’s ability to form hydrogen bonds was changed. So, the main force in the interaction between polyphenols and blood proteins is the hydrophobic force and not hydrogen bonds. It could be that as glucose alters a protein’s structure, it is this hydrophobic interaction that is altered, decreasing the binding affinity.

Ann Hagerman, an expert in the interactions of proteins and polyphenols and their bioactivity at Miami University, US, says that as research has been focused for many years on unmodified proteins, seeing how such modifications affect the interaction is quite interesting. She would like to see the work extended to other small molecules, using methods in addition to fluorescence spectroscopy to study the interactions.

Xiao’s team will now investigate why hydrophobic polyphenols cause a larger difference between the binding affinities of healthy and type II diabetes plasma proteins. The findings may affect the use of polyphenols in diabetes therapies, they say.

Glycation of plasma proteins in type II diabetes lowers the non-covalent interaction affinities for dietary polyphenols
Yixie Xie, Jianbo Xiao, Guoyin Kai and Xiaoqing Chen
DOI: 10.1039/C2IB00185C

Read the original article at Chemistry World

US scientists can now control the reactions occurring inside cells. The technology could lead to the manipulation of cell functions in the future, they say. Cells could be triggered to release a therapeutic protein at disease sites, or could be stimulated to regenerate tissue, in response to external cues.

‘Cells respond to cues in their environment that influence or regulate their behaviour,’ explains Milan Mrksich from the University of Chicago who, together with Rafe Petty, carried out the work. ‘This is done by protein receptors on the cell surface that interact with ligands in the extracellular environment [outside the cell].’ For example, stem cells receive cues from growth factor proteins to become a particular cell type – a nerve, bone or skin cell.

Mrksich and Petty created cell-surface protein receptors and threaded them through a cell membrane so that the receptor was outside the cell and the protein within the cell. The team designed ligands to initiate and control phosphorylation reactions in the cell. ‘We could use this mechanism to signal a phosphorylation change in the receptor, which would be the first step in a series of molecular events that would lead to a change in cell function,’ says Mrksich.

Normally, when ligands are introduced to a cell, they bind to the receptors, causing them to dimerise. This brings the receptors closer together so that, with the aid of an enzyme already present in the cell, the proteins can phosphorylate each other. To control this effect, the researchers prepared a bead a couple of microns in size and attached the ligands to its surface, fixing them in place. As the ligands bound to the receptors, many receptors were brought closer together, increasing the phosphorylation rate.

‘The experiments provide further confirmation for the central role of ligand induced receptor dimerisation in cell signalling across the cell membrane,’ says Joseph Schlessinger, professor of pharmacology from the school of medicine at Yale University, US. But, he adds that research on how to make the synthetic receptor approach commercially viable is needed.

In the future, Mrksich hopes to regulate gene expression. If you can turn on or turn off the expression of a set of genes in a cell, you could control the cell function, he says. ‘So if we wanted to regulate gene expression in an animal, we could transplant cells that were engineered with our strategies with these protein receptors into an animal, have those cells function normally within the animal tissue in which they are inserted and then, when the cells see the cues that they are engineered to respond to, they would selectively take on a new function,’ he adds.

To read Elinor Richard’s original article see Chemistry World or read the full paper here:

De novo motif for kinase mediated signaling across the cell membrane
Rafe T. Petty and Milan Mrksich
Integr. Biol., 2011, Advance Article
DOI: 10.1039/C1IB00009H