{"71815":{"#nid":"71815","#data":{"type":"news","title":"Evidence of \u0027Memory\u0027 Seen in Cells \u0026 Molecules","body":[{"value":"\u003Cp\u003EResearch reported October 29 in the online version of the journal \u003Cem\u003EProceedings of the National Academy of Sciences \u003C\/em\u003E(PNAS) provides evidence that some molecular interactions on cell surfaces may have a \u0027memory\u0027 that affects their future interactions.  The report could lead to a re-examination of results from certain single-molecule research.  \u003C\/p\u003E\n\u003Cp\u003EResearchers who use sequentially repeated tests to obtain statistical samples of molecular properties usually assume that each test is identical to - and independent of - any other tests in the sequence.  In their article, however, researchers at the Georgia Institute of Technology provide examples of test sequences that may not be composed of independent and identically-distributed (i.i.d.) random variables.\n\u003C\/p\u003E\n\u003Cp\u003E\u0022If you are probing a cell to get a bit of information, how do you know that the cell is not going to respond by changing the information it reveals the next time you probe it?\u0022 asked Cheng Zhu, a Regents\u0027 Professor in the Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.  \u0022If you are probing a molecule, can you assume that the molecule will return to its original configuration before you test it the next time?  We didn\u0027t think about this until we had been doing these kinds of experiments for more than ten years.\u0022\n\u003C\/p\u003E\n\u003Cp\u003ESupported by the National Institutes of Health, the research demonstrates that certain cells can \u0027remember\u0027 their earlier encounters through specific receptor-ligand interactions. That would mean that some sequential measurements may not have been truly independent, and could therefore prompt re-examination of some research that obtained data under the i.i.d. assumption.  \n\u003C\/p\u003E\n\u003Cp\u003E\u0022People doing research in this area ought to look at what we have found to see if their systems also have memories that may have affected their conclusions,\u0022 Zhu said.  \u0022They may discover new aspects that may have been overlooked.\u0022\n\u003C\/p\u003E\n\u003Cp\u003EUsing a micropipette adhesion frequency assay, Zhu\u0027s research team studied a number of receptor-ligand interactions.  The sequence data analysis conducted by Veronika Zarnitsyna, a research scientist in the Coulter Department, revealed examples in which an interaction observed in one test affected the outcome of a future test.  Depending on the biological system, the effect could either increase or decrease the likelihood of a future interaction.  \n\u003C\/p\u003E\n\u003Cp\u003EFor instance, interaction between T cell receptors and an antigen bound to major histocompatibility molecules showed positive correlation, with one interaction increasing the likelihood of a future interaction.  Interaction between C-adherins exhibited the opposite behavior, with one interaction reducing the likelihood of a future interaction.  In a third system the researchers studied, the events appeared to be truly independent, with one interaction not affecting a future one.\n\u003C\/p\u003E\n\u003Cp\u003E\u0022The i.i.d. assumption in single-molecule experiments was something that people usually took for granted,\u0022 Zarnitsyna said.\n\u003C\/p\u003E\n\u003Cp\u003EThe research reported in PNAS began when Jun Huang, a graduate student in the Zhu lab, examined T cell test data and noted a distinct difference: interactions appeared consecutively in long strings and then disappeared for a long while.  Huang asked Zhu about the pattern.  Zhu then shared his concerns about the independence of the tests with Zarnitsyna, a biophysicist.\n\u003C\/p\u003E\n\u003Cp\u003EZarnitsyna analyzed data generated by Huang and Fang Zhang - another graduate student in the Zhu lab - and additional data obtained in the lab by Yuan-Hung Chien, a student from the laboratory of Deborah Leckband at the University of Illinois at Urbana-Champaign.\n\u003C\/p\u003E\n\u003Cp\u003E\u0022Positive memory increases the likelihood of having two interactions in a row, which generates long strings of interactions,\u0022 said Zarnitsyna.  \u0022The negative memory, conversely, decreases the likelihood of having consecutive interactions, which results in more solitary interactions in the sequence.\u0022\n\u003C\/p\u003E\n\u003Cp\u003EZhu compares the negative correlation to the effects of strong light on the eyes.  \u0022If you go from the dark to the bright, time is required before you can see well again,\u0022 he noted.  \u0022Exposure to strong light temporarily inhibits the eyes\u0027 response to the next input.\u0022\n\u003C\/p\u003E\n\u003Cp\u003EZhu\u0027s research team studies single-molecule mechanics using sensitive force techniques, such as atomic force microscopes and biomembrane force probes, to put cells and molecules together and then measure the forces or times required to pull them apart.  Ideas developed for the adhesion frequency assay may also be applicable to this research because the i.i.d. assumption is violated if the force or time depends on where in a test sequence it was measured.  \n\u003C\/p\u003E\n\u003Cp\u003EAs a next step, Zhu would like to further characterize the memory effect to determine how long it lasts.  \u0022It seems reasonable that if you prolong the cycle time - the period between trials - the cell or molecule would gradually forget\u0022 said.  \n\u003C\/p\u003E\n\u003Cp\u003EHe would also like to study the biological mechanisms of the memory effects. \n\u003C\/p\u003E\n\u003Cp\u003E\u0022We believe this phenomenon may be biologically important, though we don\u0027t yet know the implications for it,\u0022 Zhu said.  \u0022This may represent a way for cells to regulate their adhesion and signaling.  For T cells, the ability to \u0027remember\u0027 even a brief interaction with a pathogen may be related to their ability to tell an intruder from \u0027self\u0027 molecules, which is crucial to the body\u0027s defense in the immune system.\u0022\n\u003C\/p\u003E\n\u003Cp\u003E\u003Cstrong\u003EResearch News \u0026amp; Publications Office\u003Cbr \/\u003E\nGeorgia Institute of Technology\u003Cbr \/\u003E\n75 Fifth Street, N.W., Suite 100\u003Cbr \/\u003E\nAtlanta, Georgia  30308  USA\u003C\/strong\u003E\n\u003C\/p\u003E\n\u003Cp\u003E\u003Cstrong\u003EMedia Relations Contacts\u003C\/strong\u003E: John Toon (404-894-6986); E-mail: (\u003Ca href=\u0022mailto:jtoon@gatech.edu\u0022\u003Ejtoon@gatech.edu\u003C\/a\u003E) or Abby Vogel (404-385-3364); E-mail: (\u003Ca href=\u0022mailto:avogel@gatech.edu\u0022\u003Eavogel@gatech.edu\u003C\/a\u003E).\n\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":[{"value":"Researchers study assumption of independence in test sequences"}],"field_summary":[{"value":"Research reported October 29 in the online version of the journal Proceedings of the National Academy of Sciences (PNAS) provides evidence that some molecular interactions on cell surfaces may have a \u0027memory\u0027 that affects their future interactions.","format":"limited_html"}],"field_summary_sentence":[{"value":"Researchers examine single-molecule tests"}],"uid":"27303","created_gmt":"2007-10-29 00:00:00","changed_gmt":"2016-10-08 03:03:24","author":"John Toon","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2007-10-29T00:00:00-04:00","iso_date":"2007-10-29T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"hg_media":{"71816":{"id":"71816","type":"image","title":"biomembrane force probe","body":null,"created":"1449177405","gmt_created":"2015-12-03 21:16:45","changed":"1475894644","gmt_changed":"2016-10-08 02:44:04"},"71817":{"id":"71817","type":"image","title":"Cheng Zhu","body":null,"created":"1449177405","gmt_created":"2015-12-03 21:16:45","changed":"1475894644","gmt_changed":"2016-10-08 02:44:04"}},"media_ids":["71816","71817"],"related_links":[{"url":"http:\/\/www.bme.gatech.edu\/","title":"Wallace H. Coulter Department of Biomedical Engineering"},{"url":"http:\/\/www.bme.gatech.edu\/facultystaff\/faculty_record.php?id=4","title":"Cheng Zhu"}],"groups":[{"id":"1188","name":"Research Horizons"}],"categories":[{"id":"146","name":"Life Sciences and Biology"},{"id":"135","name":"Research"}],"keywords":[{"id":"7437","name":"adhesion"},{"id":"532","name":"cell"},{"id":"7536","name":"independence"},{"id":"2071","name":"molecule"}],"core_research_areas":[],"news_room_topics":[],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cstrong\u003EJohn Toon\u003C\/strong\u003E\u003Cbr \/\u003EResearch News \u0026amp; Publications Office\u003Cbr \/\u003E\u003Ca href=\u0022http:\/\/www.gatech.edu\/contact\/index.html?id=jt7\u0022\u003EContact John Toon\u003C\/a\u003E\u003Cbr \/\u003E\u003Cstrong\u003E404-894-6986\u003C\/strong\u003E","format":"limited_html"}],"email":["jtoon@gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}