{"281681":{"#nid":"281681","#data":{"type":"news","title":"Biomolecular Tweezers Facilitate Study of Mechanical Force Effects on Cells and Proteins","body":[{"value":"\u003Cp\u003EA new type of biomolecular tweezers could help researchers study how mechanical forces affect the biochemical activity of cells and proteins. The devices \u2013 too small to see without a microscope \u2013 use opposing magnetic and electrophoretic forces to precisely stretch the cells and molecules, holding them in position so that the activity of receptors and other biochemical activity can be studied.\u003C\/p\u003E\u003Cp\u003EArrays of the tweezers could be combined to study multiple molecules and cells simultaneously, providing a high-throughput capability for assessing the effects of mechanical forces on a broad scale. Details of the devices, which were developed by researchers at the Georgia Institute of Technology and Emory University in Atlanta, were published February 19, 2014, in the journal \u003Cem\u003ETechnology\u003C\/em\u003E.\u003C\/p\u003E\u003Cp\u003E\u201cOur lab has been very interested in mechanical-chemical switches in the extracellular matrix, but we currently have a difficult time interrogating these mechanisms and discovering how they work in vivo,\u201d said \u003Ca href=\u0022http:\/\/www.bme.gatech.edu\/facultystaff\/faculty_record.php?id=96\u0022\u003EThomas Barker\u003C\/a\u003E, an associate professor in the \u003Ca href=\u0022http:\/\/www.bme.gatech.edu\/\u0022\u003EWallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University\u003C\/a\u003E. \u201cThis device could help biologists and biomedical engineers answer questions that cannot be answered right now.\u201d\u003C\/p\u003E\u003Cp\u003EFor example, a cell that\u2019s binding the extracellular matrix may bind with one receptor while the matrix is being stretched, and a different receptor when it\u2019s not under stress. Those binding differences could drive changes in cell phenotype and affect processes such as cell differentiation. But they are now difficult to study.\u003C\/p\u003E\u003Cp\u003E\u201cHaving a device like this will allow us to interrogate what the specific binding sites are and what the specific binding triggers are,\u201d Barker explained. \u201cRight now, we know very little about this area when it comes to protein biochemistry.\u201d\u003C\/p\u003E\u003Cp\u003EScientists have been able to study how single cells or proteins are affected by mechanical forces, but their activity can vary considerably from cell-to-cell and among molecules. The new tweezers, which are built using nanolithography, can facilitate studying thousands or more cells and proteins in aggregate. The researchers are currently testing prototype 15 by 15 arrays which they believe could be scaled up.\u003C\/p\u003E\u003Cp\u003E\u201cFor me, it\u2019s not sufficient to pull and hold onto a single protein,\u201d said Barker. \u201cI have to pull and hold onto tens of thousands of proteins to really use the technologies we have to develop molecular probes.\u201d\u003C\/p\u003E\u003Cp\u003EAt the center of the tweezers are 2.8- micron polystyrene microbeads that contain superparamagnetic nanoparticles. The tiny beads are engineered to adhere to a sample being studied. That sample is attached to a bead on one side, and to a magnetic pad on the other. The magnet draws the bead toward it, while an electrophoretic force created by current flowing through a gold wiring pattern pushes the bead away.\u003C\/p\u003E\u003Cp\u003E\u201cThe device simultaneously pushes and pulls on the same particle,\u201d Barker explained. \u201cThis allows us to hold the sample at a very specific position above the magnet.\u201d\u003C\/p\u003E\u003Cp\u003EBecause the forces can be varied, the tweezers can be used to study structures of widely different size scales, from protein molecules to cells \u2013 a size difference of approximately a thousand times, noted \u003Ca href=\u0022http:\/\/www.bme.gatech.edu\/facultystaff\/faculty_record.php?id=152\u0022\u003EWilbur Lam\u003C\/a\u003E, an assistant professor in the Coulter Department. Absolute forces in the nano-Newton range applied by the two sources overcome the much smaller effects of Brownian motion and thermal energy, allowing the tweezers to hold the cells or molecules without constant adjustment.\u003C\/p\u003E\u003Cp\u003E\u201cWe are basically leveraging microchip technology that has been developed by electrical and mechanical engineers,\u201d Lam noted. \u201cWe are able to leverage these very tiny features that enable us to create a very sharp electrical field on one end against an opposing short magnetic field. Because there are two ways of controlling it, we have tight resolution and can get to many different scales.\u201d\u003C\/p\u003E\u003Cp\u003EAs a proof of principle for the system, the researchers demonstrated its ability to distinguish between antigen binding to loaded magnetic beads coated with different antibodies. When a sufficient upward force is applied, non-specific antibody coated beads are displaced from the antigen-coated device surface, while beads coated with the specific antibody are more strongly attracted to the surface and retained on it.\u003C\/p\u003E\u003Cp\u003EBarker and Lam began working together on the tweezers three years ago when they realized they had similar interests in studying the effects of mechanical action on different biological systems.\u003C\/p\u003E\u003Cp\u003E\u201cWe shouldn\u2019t be surprised that biology can be dictated by physical parameters,\u201d Lam explained. \u201cEverything has to obey the laws of physics, and mechanics gets to the heart of that.\u201d\u003C\/p\u003E\u003Cp\u003ELam\u2019s interest is at the cellular scale, specifically in blood cells.\u003C\/p\u003E\u003Cp\u003E\u201cBlood cells also respond differently, biologically, when you squeeze them and when you stretch them,\u201d he said. \u201cFor instance, we have learned that mechanics has a lot to do with atherosclerosis, but the systems we currently have for studying this mechanism can only look at single-cell events. If you can look at many cells at once, you get a much better statistical view of what\u2019s happening.\u201d\u003C\/p\u003E\u003Cp\u003EBarker\u2019s interests, however, are at the molecular level.\u003C\/p\u003E\u003Cp\u003E\u201cWe are primarily interested in evolving antibodies that are capable of distinguishing different force-mediated conformations of proteins,\u201d he explained. \u201cWe have a specific protein that we are interested in, but this technique could be applied to any proteins that are suspected to have these force-activated changes in their biochemical activity.\u201d\u003C\/p\u003E\u003Cp\u003EWhile the tweezers meet the specific experimental needs of Lam and Barker, the researchers hope to find other applications. The tweezers were developed in collaboration with graduate student Lizhi Cao and post-doctoral fellow Zhengchun Peng.\u003C\/p\u003E\u003Cp\u003E\u201cBecause of the scale we are able to examine \u2013 both molecular and cellular \u2013 I think this will have a lot of applications both in protein molecular engineering and biotechnology,\u201d Lam said. \u201cThis could be a useful way for people to screen relevant molecules because there currently aren\u2019t good ways to do that.\u201d\u003C\/p\u003E\u003Cp\u003EBeyond biological systems, the device could be used in materials development, microelectronics and even sensing.\u003C\/p\u003E\u003Cp\u003E\u201cThis ability to detect discrete binding and unbinding events between molecular species is of high interest right now,\u201d Barker added. \u201cBiosensor applications come out of this naturally.\u201d\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ECITATION\u003C\/strong\u003E: Lizhi Cao, et al., \u201cA combined magnetophoresis\/dielectrophoresis based microbead array as a high-throughput biomolecular tweezers,\u201d (Technology 2014). \u003Ca href=\u0022http:\/\/dx.doi.org\/10.1142\/S2339547814500058\u0022\u003Ehttp:\/\/dx.doi.org\/10.1142\/S2339547814500058\u003C\/a\u003E\u003Cbr \/\u003E\u003Cbr \/\u003E\u003Cstrong\u003EResearch News \u003C\/strong\u003E\u003Cbr \/\u003E\u003Cstrong\u003EGeorgia Institute of Technology\u003C\/strong\u003E\u003Cbr \/\u003E\u003Cstrong\u003E177 North Avenue\u003C\/strong\u003E\u003Cbr \/\u003E\u003Cstrong\u003EAtlanta, Georgia\u0026nbsp; 30332-0181\u0026nbsp; USA\u003C\/strong\u003E\u003Cbr \/\u003E\u003Cbr \/\u003E\u003Cstrong\u003EMedia Relations Contacts\u003C\/strong\u003E: John Toon (404-894-6986) (\u003Ca href=\u0022mailto:jtoon@gatech.edu\u0022\u003Ejtoon@gatech.edu\u003C\/a\u003E) or Brett Israel (404-385-1933) (\u003Ca href=\u0022mailto:brett.israel@comm.gatech.edu\u0022\u003Ebrett.israel@comm.gatech.edu\u003C\/a\u003E).\u003Cbr \/\u003E\u003Cstrong\u003EWriter\u003C\/strong\u003E: John Toon\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003EA new type of biomolecular tweezers could help researchers study how mechanical forces affect the biochemical activity of cells and proteins. The devices \u2013 too small to see without a microscope \u2013 use opposing magnetic and electrophoretic forces to precisely stretch the cells and molecules, holding them in position so that the activity of receptors and other biochemical activity can be studied.\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"A new type of biomolecular tweezers could help researchers study how mechanical forces affect the biochemical activity of cells and proteins."}],"uid":"27303","created_gmt":"2014-03-09 14:27:14","changed_gmt":"2016-10-08 03:15:58","author":"John Toon","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2014-03-10T00:00:00-04:00","iso_date":"2014-03-10T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"hg_media":{"281661":{"id":"281661","type":"image","title":"Biomolecular tweezers","body":null,"created":"1449244199","gmt_created":"2015-12-04 15:49:59","changed":"1475894976","gmt_changed":"2016-10-08 02:49:36","alt":"Biomolecular tweezers","file":{"fid":"198943","name":"molecular-tweezers.jpg","image_path":"\/sites\/default\/files\/images\/molecular-tweezers_0.jpg","image_full_path":"http:\/\/tlwarc.hg.gatech.edu\/\/sites\/default\/files\/images\/molecular-tweezers_0.jpg","mime":"image\/jpeg","size":1038763,"path_740":"http:\/\/tlwarc.hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/molecular-tweezers_0.jpg?itok=i0NcQFTl"}},"281651":{"id":"281651","type":"image","title":"Biomolecular tweezers figure","body":null,"created":"1449244199","gmt_created":"2015-12-04 15:49:59","changed":"1475894976","gmt_changed":"2016-10-08 02:49:36","alt":"Biomolecular tweezers figure","file":{"fid":"198942","name":"biomolecular-tweezers-figure_1.jpg","image_path":"\/sites\/default\/files\/images\/biomolecular-tweezers-figure_1_0.jpg","image_full_path":"http:\/\/tlwarc.hg.gatech.edu\/\/sites\/default\/files\/images\/biomolecular-tweezers-figure_1_0.jpg","mime":"image\/jpeg","size":821807,"path_740":"http:\/\/tlwarc.hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/biomolecular-tweezers-figure_1_0.jpg?itok=d7d1VRJH"}},"281671":{"id":"281671","type":"image","title":"Biomolecular tweezers researchers","body":null,"created":"1449244199","gmt_created":"2015-12-04 15:49:59","changed":"1475894976","gmt_changed":"2016-10-08 02:49:36","alt":"Biomolecular tweezers researchers","file":{"fid":"198944","name":"molecular-tweezers-researchers.jpg","image_path":"\/sites\/default\/files\/images\/molecular-tweezers-researchers_0.jpg","image_full_path":"http:\/\/tlwarc.hg.gatech.edu\/\/sites\/default\/files\/images\/molecular-tweezers-researchers_0.jpg","mime":"image\/jpeg","size":1767612,"path_740":"http:\/\/tlwarc.hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/molecular-tweezers-researchers_0.jpg?itok=QiIpHXz3"}}},"media_ids":["281661","281651","281671"],"groups":[{"id":"1188","name":"Research Horizons"}],"categories":[{"id":"146","name":"Life Sciences and Biology"},{"id":"135","name":"Research"}],"keywords":[{"id":"3056","name":"biochemical"},{"id":"88571","name":"biomolecular tweezers"},{"id":"88581","name":"electrophoresis"},{"id":"62101","name":"mechanical force"},{"id":"14574","name":"Thomas Barker"},{"id":"3264","name":"Wallace H. Coulter Department of Biomedical Engineering"},{"id":"14681","name":"Wilbur Lam"}],"core_research_areas":[{"id":"39441","name":"Bioengineering and Bioscience"},{"id":"39451","name":"Electronics and Nanotechnology"}],"news_room_topics":[{"id":"71891","name":"Health and Medicine"}],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003EJohn Toon\u003C\/p\u003E\u003Cp\u003EResearch News\u003C\/p\u003E\u003Cp\u003E(404) 894-6986\u003C\/p\u003E\u003Cp\u003E\u003Ca href=\u0022mailto:jtoon@gatech.edu\u0022\u003Ejtoon@gatech.edu\u003C\/a\u003E\u003C\/p\u003E","format":"limited_html"}],"email":["jtoon@gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}