{"192341":{"#nid":"192341","#data":{"type":"news","title":"Sticky Cells: Cyclic Mechanical Reinforcement Extends Longevity of Bonds Between Cells","body":[{"value":"\u003Cp\u003EResearch carried out by scientists at the Georgia Institute of Technology and The University of Manchester has revealed new insights into how cells stick to each other and to other bodily structures, an essential function in the formation of tissue structures and organs. It\u2019s thought that abnormalities in their ability to do so play an important role in a broad range of disorders, including cardiovascular disease and cancer.\u003C\/p\u003E\u003Cp\u003EThe study\u2019s findings are outlined in the journal \u003Cem\u003EMolecular Cell\u003C\/em\u003E and describe a surprising new aspect of cell adhesion involving the family of cell adhesion molecules known as integrins, which are found on the surfaces of most cells. The research uncovered a phenomenon termed \u201ccyclic mechanical reinforcement,\u201d in which the length of time during which bonds exist is extended with repeated pulling and release between the integrins and ligands that are part of the extracellular matrix to which the cells attach.\u003C\/p\u003E\u003Cp\u003EProfessor Martin Humphries, dean of the faculty of life sciences at the University of Manchester and one of the paper\u2019s co-authors, says the study suggests some new capabilities for cells: \u201cThis paper identifies a new kind of bond that is strengthened by cyclical applications of force, and which appears to be mediated by complex shape changes in integrin receptors. The findings also shed light on a possible mechanism used by cells to sense extracellular topography and to aggregate information through \u2018remembering\u2019 multiple interaction events.\u201d\u003C\/p\u003E\u003Cp\u003EThe cyclic mechanical reinforcement allows force to prolong the lifetimes of bonds, demonstrating a mechanical regulation of receptor-ligand interactions and identifying a molecular mechanism for strengthening cell adhesion through cyclical forces.\u003C\/p\u003E\u003Cp\u003E\u201cMany cell functions such as differentiation, growth and the expression of particular genes depend on cell interaction with the ligands of the intracellular matrix,\u201d said Cheng Zhu, a professor in the Coulter Department of Biomedical Engineering at Georgia Tech and Emory University and the study\u2019s corresponding author.\u0026nbsp; \u201cThe cells respond to their environment, which includes many mechanical aspects. This study has extended our understanding of how connections are made and how mechanical forces regulate interactions.\u201d\u003C\/p\u003E\u003Cp\u003EThe research was published online by the journal on February 14th. The work was supported by the National Institutes of Health (NIH) and the Wellcome Trust.\u003C\/p\u003E\u003Cp\u003ECells of the body regulate adhesion in response to both internally- and externally-applied forces. This is particularly important to adhesion mediated by proteins such as integrins that connect the extracellular matrix to the cytoskeleton \u2013 and provide cells with both mechanical anchorages and the means to initiate signaling.\u003C\/p\u003E\u003Cp\u003EUsing delicate force measuring equipment, researchers in Zhu\u2019s lab and the laboratory of Andres Garcia \u2013 a professor in the Woodruff School of Mechanical Engineering at Georgia Tech \u2013 collaborated to study adhesion between integrin and fibronectin, a protein component of the extracellular matrix. What they found was that cyclic forces applied to the bond switch it from a short lived state \u2013 with lifetimes of about one second \u2013 to a long-lived state that can exist for more than a hundred seconds.\u003C\/p\u003E\u003Cp\u003E\u201cForce can be very important in biology,\u201d said Zhu. \u201cForce has direction, magnitude and duration, so in describing its effects on biological systems, you have to use a more complete language.\u201d\u003C\/p\u003E\u003Cp\u003EZhu, Garcia and Georgia Tech graduate students Fang Kong, William Parks and David Dumbauld \u2013 along with postdoctoral fellow Zenhai Li \u2013 used two different mechanical techniques to study the strength of bonds between integrin and fibronectin. One technique measured the bond strengths in purified molecules, while the other studied the effects of them in their native cellular environment.\u003C\/p\u003E\u003Cp\u003E\u201cWe have very precise force transducers that allow us to measure force on the scale of pico-newtons,\u201d said Zhu. \u201cWe prepare the samples in such a way that we engage only one bond, then we control the application of force and observe what happens.\u201d\u003C\/p\u003E\u003Cp\u003EThe researchers first used an atomic force microscope to bring the integrin molecule together with the fibronectin, then separate the two. Instruments measured the pico-newton forces required to separate the molecules, and found that the duration of the bonds increased with the repetition of the contacts.\u003C\/p\u003E\u003Cp\u003EThe second technique, known as BFP, involved the use of a fibronectin-bearing glass bead attached to a red blood cell aspirated by a micropipette. Integrin expressed on the micropipette-aspirated cell was pressed into the bead, then pulled away over repeated cycles.Lifetime measurement confirmed that repeated pulling increased the longevity of the bonds.\u003C\/p\u003E\u003Cp\u003EThe researchers studied two integrins, part of a family of 24 related molecules that operate in humans. In future work, they hope to determine whether or not the cyclic mechanical reinforcement they observed is a universal property of many cellular adhesion molecules.\u003C\/p\u003E\u003Cp\u003EThe researchers also hope to explore how cells use this cyclic mechanical reinforcement. Because many disease processes result from abnormal cellular adhesion mechanisms, a better understanding could provide insights into how cardiovascular disease, cancer and immune system disorders operate.\u003C\/p\u003E\u003Cp\u003E\u201cThe findings of the paper have deep implications for our understanding of force-regulated signaling,\u201d added Humphries. \u201cThere is abundant biological evidence for profound effects of extracellular tensility and elasticity in controlling processes such as cancer cell proliferation and stem cell differentiation, but the mechanisms whereby this information is transduced across the outer cell membrane are unclear.\u201d\u003C\/p\u003E\u003Cp\u003E\u003Cem\u003EThis research was supported by the National Institutes of Health (NIH) under grants AI44902 and GM065918. The conclusions are those of the authors and do not necessarily represent the official views of the NIH.\u003C\/em\u003E\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ECITATION\u003C\/strong\u003E: Kong, F., et al., Cyclic Mechanical Reinforcement of Integrin-Ligand Interactions, Molecular Cell (2013). \u003Ca href=\u0022http:\/\/dx.doi.org\/10.1016\/j.molcel.2013.01.015\u0022 title=\u0022http:\/\/dx.doi.org\/10.1016\/j.molcel.2013.01.015\u0022\u003Ehttp:\/\/dx.doi.org\/10.1016\/j.molcel.2013.01.015\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\u0026nbsp; 30332-0181\u0026nbsp; USA\u003C\/strong\u003E\u003Cbr \/\u003E\u003Cbr \/\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).\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EWriter\u003C\/strong\u003E: John Toon\u003C\/p\u003E\u003Cp\u003E\u0026nbsp;\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003EA new study provides insights into how cells stick to each other and to other bodily structures, an essential function in the formation of tissue structures and organs. It\u2019s thought that abnormalities in their ability to do so play an important role in a broad range of disorders.\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"A new study provides insights into how cells stick to each other and to other bodily structures."}],"uid":"27303","created_gmt":"2013-02-14 18:32:37","changed_gmt":"2016-10-08 03:13:37","author":"John Toon","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2013-02-14T00:00:00-05:00","iso_date":"2013-02-14T00:00:00-05:00","tz":"America\/New_York"},"extras":[],"hg_media":{"192301":{"id":"192301","type":"image","title":"Cyclic Mechanical Reinforcement","body":null,"created":"1449179879","gmt_created":"2015-12-03 21:57:59","changed":"1475894841","gmt_changed":"2016-10-08 02:47:21","alt":"Cyclic Mechanical Reinforcement","file":{"fid":"196308","name":"cyclic-mechanical22.jpg","image_path":"\/sites\/default\/files\/images\/cyclic-mechanical22_1.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/cyclic-mechanical22_1.jpg","mime":"image\/jpeg","size":1648073,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/cyclic-mechanical22_1.jpg?itok=BU_yHZ2C"}},"192321":{"id":"192321","type":"image","title":"Cyclic Mechanical Reinforcement2","body":null,"created":"1449179879","gmt_created":"2015-12-03 21:57:59","changed":"1475894841","gmt_changed":"2016-10-08 02:47:21","alt":"Cyclic Mechanical Reinforcement2","file":{"fid":"196310","name":"cyclic-mechanical130.jpg","image_path":"\/sites\/default\/files\/images\/cyclic-mechanical130_1.jpg","image_full_path":"http:\/\/hg.gatech.edu\/\/sites\/default\/files\/images\/cyclic-mechanical130_1.jpg","mime":"image\/jpeg","size":1483223,"path_740":"http:\/\/hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/cyclic-mechanical130_1.jpg?itok=ypbeA3zd"}}},"media_ids":["192301","192321"],"groups":[{"id":"1188","name":"Research Horizons"}],"categories":[{"id":"146","name":"Life Sciences and Biology"}],"keywords":[{"id":"539","name":"Andres Garcia"},{"id":"58461","name":"cell adhesion"},{"id":"58491","name":"cell bonds"},{"id":"9893","name":"Cheng Zhu"},{"id":"14219","name":"Coulter Department of Biomedical Engineering"},{"id":"58451","name":"integrin"},{"id":"167377","name":"School of Mechanical Engineering"}],"core_research_areas":[{"id":"39441","name":"Bioengineering and Bioscience"}],"news_room_topics":[],"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":""}}}