{"496271":{"#nid":"496271","#data":{"type":"news","title":"Physics: It\u0027s What\u0027s Happening Inside Your Body Right Now","body":[{"value":"\u003Cp\u003ESimple physics may play a larger role than previously thought in helping control key bodily processes \u2013 such as how the body fights infection.\u003C\/p\u003E\u003Cp\u003EUsing a model blood vessel system built on a polymer microchip, researchers have shown that the relative softness of white blood cells determines whether they remain in a dormant state along vessel walls or enter blood circulation to fight infection. Changes in these cell mechanical properties \u2013 from stiff to soft \u2013 can be triggered as a side effect of drugs commonly used to fight inflammation or boost blood pressure.\u003C\/p\u003E\u003Cp\u003EOther researchers have found that blood flow affects the cells that line arteries and that particles within cells tend to congregate near cell walls. Better understanding the role of physics in fine-tuning such biological processes could give researchers new approaches for both diagnosing and treating disease.\u003C\/p\u003E\u003Cp\u003EThe work, believed the first to show how biophysical effects can control where white blood cells are located within the blood circulation, was reported February 8 in the journal \u003Cem\u003EProceedings of the National Academy of Sciences\u003C\/em\u003E. The research was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH), the National Science Foundation (NSF), and the American Heart Association.\u003C\/p\u003E\u003Cp\u003E\u201cWe are showing that white blood cells, also known as leukocytes, respond physically to these drugs and that there is a biological consequence to that response,\u201d said \u003Ca href=\u0022https:\/\/bme.gatech.edu\/bme\/faculty\/Wilbur-A.-Lam\u0022\u003EWilbur Lam\u003C\/a\u003E, an assistant professor in the \u003Ca href=\u0022http:\/\/www.bme.gatech.edu\/\u0022\u003EWallace H. Coulter Department of Biomedical Engineering\u003C\/a\u003E at Georgia Tech and Emory University. \u201cThis may suggest new ways to treat disease, and new places to look for diagnostic information. There may be physics-based disease biomarkers that we can use in addition to the common biological and biochemical markers we have been using.\u201d\u003C\/p\u003E\u003Cp\u003ELam\u2019s research group began studying the issue to better understand a common side effect of glucocorticoid drugs such as hydrocortisone used to treat inflammatory disorders such as asthma and allergic reactions. These hormonal drugs prompt an increase in white blood cell counts, a change that had been attributed to biological processes, including a reduced \u201cstickiness\u201d between the cells and blood vessel walls. The increase in white cell count is also seen with drugs that support blood pressure, such as epinephrine, also known as adrenaline.\u003C\/p\u003E\u003Cp\u003E\u201cThe biological explanation for this seemed to fall short, so we thought maybe some of what was happening could be attributed to other factors \u2013 such as physical and mechanical issues,\u201d said Lam, who is also a physician in the Aflac Cancer and Blood Disorders Center at Children\u2019s Healthcare of Atlanta and the Department of Pediatrics at the Emory University School of Medicine.\u003C\/p\u003E\u003Cp\u003ETo examine the theory, graduate student Meredith Fay and postdoctoral researcher David Myers fabricated model blood vessel systems that include artificial blood vessels with diameters as narrow as the smallest capillaries in the body. To isolate effects attributable only to physics, the systems \u2013 which were fabricated in Georgia Tech\u2019s \u003Ca href=\u0022http:\/\/www.ien.gatech.edu\/\u0022\u003EInstitute for Electronics and Nanotechnology\u003C\/a\u003E \u2013 did not include the endothelial cells that normally line blood vessels in the body.\u003C\/p\u003E\u003Cp\u003EUsing blood samples taken from a healthy human volunteer, they studied the behavior of white blood cells in the presence \u2013 and absence \u2013 of the drugs dexamethasone \u2013 a glucocorticoid drug \u2013 and epinephrine. Working with Georgia Tech Professor of Mechanical Engineering Todd Sulchek, they also used atomic force microscopy to characterize the stiffness of individual white blood cells before and after they had been exposed to the drugs, and determined that the drugs cause the cells to become significantly softer than before exposure.\u003C\/p\u003E\u003Cp\u003E\u201cWhen we fluorescently label the white blood cells and perfuse them into the artificial vessels, the white blood cells are always flowing along the edge, on the walls of these artificial blood vessels,\u201d said Lam. \u201cBut when they are exposed to the drugs, they go to the center of the channel and enter the main blood flow. Then, we discovered that the drugs cause the cells to remodel actin, which comprises the \u2018skeleton\u2019 of all mammalian cells.\u201d\u003C\/p\u003E\u003Cp\u003EThe group\u2019s overall hypothesis is that the body uses the mechanical properties of these cells to help control their activity and where they are located within the circulation. The relative softness or stiffness of the cells, which collide constantly with billions of other cells in the bloodstream, including red and white blood cells, causes the cells to self-sort and determines where they end up physically within both the model blood vessels and in the human body.\u003C\/p\u003E\u003Cp\u003E\u201cThe soft cells are always flowing in the middle of the bloodstream, while the stiff ones are sequestered on the edges,\u201d Lam said. \u201cWe believe this is how white blood cells traffic in the body and get to the site of an infection. This may be a way that the body very efficiently sorts and directs its white blood cells to get them where they\u2019re needed.\u201d\u003C\/p\u003E\u003Cp\u003EAs a next step, Lam hopes to study how physical properties affect the movement of hematopoietic stem cells used in bone marrow transplants. Once injected intravenously into the body, the cells quickly move from the circulation to bone marrow sites where they belong, and he believes mechanical properties may also play a role in this homing process.\u003C\/p\u003E\u003Cp\u003E\u201cWhenever there is a change in some cellular activity or physiological activity, we tend to try to explain everything at the genetic level \u2013 which genes turn off and which genes turn on,\u201d he said. \u201cGene expression is a relatively complex process, and our hypothesis is that there are probably a lot of cellular processes that are much simpler and more efficient than the typical paradigm of DNA expression, then RNA translation, and then protein production. A little tweak of a white blood cell\u2019s actin will allow it to change from stiff to soft, and that small change, in and of itself, may have profound physiologic consequences and enable it to be transported from one part of the body to another.\u201d\u003C\/p\u003E\u003Cp\u003EIn addition to those already mentioned, the research also included Amit Kumar and Michael Graham from the Department of Chemical and Biological Engineering at the University of Wisconsin-Madison; Cory Turbyfield, Rebecca Byler and Kaci Crawford from the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University and the George W. Woodruff School of Mechanical Engineering at Georgia Tech; Robert Mannino, Alvin Laohapant, Erika Tyburski, Yumiko Sakurai and Micahel Rosenbluth from the Coulter Department, the AflacCancer Center and Blood Disorders Service of Children\u0027s Healthcare of Atlanta, Emory University School of Medicine, the Winship Cancer Institute at Emory University, the Parker E. Petit Institute for Bioengineering and Bioscience at Georgia Tech, and the Institute for Electronics and Nanotechnology at Georgia Tech; and Neil Switz of The Evergreen State College.\u003C\/p\u003E\u003Cp\u003E\u003Cem\u003EThis research was supported by the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH) under grant 5R01HL121264-03, the National Science Foundation (NSF) under grant CBET-1436082 and the American Heart Association. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the sponsors.\u003C\/em\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ECITATION\u003C\/strong\u003E: Meredith E. Fay, et al., \u201cCellular softening mediates leukocyte demargination and trafficking, thereby increasing clinical blood counts,\u201d (PNAS 2016). \u003Ca href=\u0022http:\/\/dx.doi.org\/10.1073\/pnas.1508920113\u0022\u003Ehttp:\/\/dx.doi.org\/10.1073\/pnas.1508920113\u003C\/a\u003E\u003C\/p\u003E\u003Cp\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 30332-0181 USA\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EMedia Relations Contact\u003C\/strong\u003E: John Toon (404-894-6986) (\u003Ca href=\u0022mailto:jtoon@gatech.edu\u0022\u003Ejtoon@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\u003EUsing a model blood vessel system built on a polymer microchip, researchers have shown that the relative softness of white blood cells determines whether they remain in a dormant state along vessel walls or enter blood circulation to fight infection.\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"Researchers have shown that the relative softness of white blood cells determines whether they remain in a dormant state."}],"uid":"27303","created_gmt":"2016-02-06 21:11:44","changed_gmt":"2016-10-08 03:20:35","author":"John Toon","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2016-02-08T00:00:00-05:00","iso_date":"2016-02-08T00:00:00-05:00","tz":"America\/New_York"},"extras":[],"hg_media":{"496251":{"id":"496251","type":"image","title":"Blood vessel on a chip2","body":null,"created":"1455120000","gmt_created":"2016-02-10 16:00:00","changed":"1475895253","gmt_changed":"2016-10-08 02:54:13","alt":"Blood vessel on a chip2","file":{"fid":"204584","name":"microfluidic-device5.jpg","image_path":"\/sites\/default\/files\/images\/microfluidic-device5_0.jpg","image_full_path":"http:\/\/www.tlwarc.hg.gatech.edu\/\/sites\/default\/files\/images\/microfluidic-device5_0.jpg","mime":"image\/jpeg","size":945783,"path_740":"http:\/\/www.tlwarc.hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/microfluidic-device5_0.jpg?itok=KpYxxX8N"}},"496241":{"id":"496241","type":"image","title":"Blood vessel on a chip","body":null,"created":"1455120000","gmt_created":"2016-02-10 16:00:00","changed":"1475895253","gmt_changed":"2016-10-08 02:54:13","alt":"Blood vessel on a chip","file":{"fid":"204583","name":"microfluidic-device6.jpg","image_path":"\/sites\/default\/files\/images\/microfluidic-device6_0.jpg","image_full_path":"http:\/\/www.tlwarc.hg.gatech.edu\/\/sites\/default\/files\/images\/microfluidic-device6_0.jpg","mime":"image\/jpeg","size":738889,"path_740":"http:\/\/www.tlwarc.hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/microfluidic-device6_0.jpg?itok=v8RDwnSf"}},"496261":{"id":"496261","type":"image","title":"Studying blood flow in microchip vessels","body":null,"created":"1455120000","gmt_created":"2016-02-10 16:00:00","changed":"1475895253","gmt_changed":"2016-10-08 02:54:13","alt":"Studying blood flow in microchip vessels","file":{"fid":"204585","name":"microfluidic-device2.jpg","image_path":"\/sites\/default\/files\/images\/microfluidic-device2_0.jpg","image_full_path":"http:\/\/www.tlwarc.hg.gatech.edu\/\/sites\/default\/files\/images\/microfluidic-device2_0.jpg","mime":"image\/jpeg","size":1547915,"path_740":"http:\/\/www.tlwarc.hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/microfluidic-device2_0.jpg?itok=a9Fta7q4"}}},"media_ids":["496251","496241","496261"],"groups":[{"id":"1188","name":"Research Horizons"}],"categories":[{"id":"146","name":"Life Sciences and Biology"},{"id":"149","name":"Nanotechnology and Nanoscience"},{"id":"135","name":"Research"},{"id":"150","name":"Physics and Physical Sciences"}],"keywords":[{"id":"1440","name":"blood"},{"id":"37591","name":"blood flow"},{"id":"25301","name":"circulation"},{"id":"171634","name":"hematology"},{"id":"10660","name":"infection"},{"id":"11008","name":"leukocyte"},{"id":"7342","name":"microchip"},{"id":"960","name":"physics"},{"id":"171635","name":"white blood cell"},{"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\u003Ca href=\u0022mailto:jtoon@gatech.edu\u0022\u003Ejtoon@gatech.edu\u003C\/a\u003E\u003C\/p\u003E\u003Cp\u003E(404) 894-6986\u003C\/p\u003E","format":"limited_html"}],"email":["jtoon@gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}