Golden membranes pave the way for a better understanding of cancerand the immune system

Football has often been called “a game of inches,” but biology is agame of nanometers, where spatial differences of only a fewnanometers can determine the fate of a cell – whether it lives ordies, remains normal or turns cancerous. Scientists with the U.S.Department of Energy (DOE)’s Lawrence Berkeley National Laboratory(Berkeley Lab) have developed a new and better way to study theimpact of spatial patterns on living cells. Berkeley Lab chemist Jay Groves led a study in which artificialmembranes made up of a fluid bilayer of lipid molecules wereembedded with fixed arrays of gold nanoparticles to control thespacing of proteins and other cellular molecules placed on themembranes. This provided the researchers with an unprecedentedopportunity to study how the spatial patterns of chemical andphysical properties on membrane surfaces influence the behavior ofcells.

“The gold nanoparticles are similar to the size of a single proteinmolecule, which gets us to a scale we couldn’t really accessbefore,” says Groves. “As the first example of a biologicalmembrane platform that combines fixed nanopatterning with themobility of fluid lipid bilayers, our technique represents animportant improvement over previous patterning methods.” Groves holds joint appointments with Berkeley Lab’s PhysicalBiosciences Division and the University of California (UC)Berkeley’s Chemistry Department, and is a Howard Hughes MedicalInstitute (HHMI) investigator. He is the corresponding author of apaper that reports these results in the journal Nano Letters. Thepaper is titled “Supported Membranes Embedded with Fixed Arrays ofGold Nanoparticles.” Spatial patterning of chemical and physical properties onartificial membranes of lipid bilayers is a time-tested way tostudy the behavior of cultured biological cells.

Natural lipidbilayer membranes surround virtually all living cells as well asmany of the structures inside the cell including the nucleus. Thesemembranes provide a barrier that restrains the movement of proteinsand other cellular molecules, penning them into their properlocations and preventing them from moving into areas where they donot belong. Past spatial patterning efforts on artificial membraneshave been done on an all-or-nothing basis – proteins placed on amembrane either had complete mobility or were fixed in a staticposition. “Immobile patterning intrinsically defeats any cellular processthat naturally involves movement,” Groves says. ND Yag Laser Machine

“On the other handwe need to be able to impose some fixed barriers in order tomanipulate membranes in really novel ways.” Groves is a recognized leader in the development of unique”supported” synthetic membranes that are constructed out of lipidsand assembled onto a substrate of solid silica. He and his grouphave used these supported membranes to demonstrate that livingcells not only interact with their environment through chemicalsignals but also through physical force. “We call our approach the spatial mutation strategy becausemolecules in a cell can be spatially re-arranged without alteringthe cell in any other way,” he says. However, until now Groves and his group were unable to get to thetens of nanometers length-scales that they can now reach byembedding their supported membranes with gold nanoparticles. “Our new membranes provide a hybrid interface consisting of mobileand immobile components with controlled geometry,” Groves says.”Proteins or other cellular molecules can be associated with thefluid lipid component, the fixed nanoparticle component, or both.” The gold nanoparticle arrays were patterned through a self-assemblyprocess that provides controllable spacing between particles in thearray in the important range of 50 to 150 nanometers. China Medical Co2 Laser

The goldnanoparticles themselves measure about five to seven nanometers indiameter. Groves and his team successfully tested their hybrid membranes on aline of breast cancer cells known as MDA-MB-231 that is highly invasive. With theirhybrid membranes, the team demonstrated that in the absence of celladhesion molecules, the membrane remained essentially free of the cancer cells, but when both the nanoparticles and the lipid werefunctionalized with molecules that promote cell adhesion, thecancer cells were found all over the surface. Groves and his research group are now using their gold nanoparticlemembranes to study both cancer metastasis and T cell immunology.They expect to report their results soon. ND Yag Laser Machine

Additional References Citations.

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