{"62095":{"#nid":"62095","#data":{"type":"news","title":"Factors Beyond Crowding Affect Molecular Motion in Cells","body":[{"value":"\u003Cp\u003EUsing large-scale computer simulations, researchers at the Georgia Institute of Technology have identified the most important factors affecting how molecules move through the crowded environment inside living cells. The findings suggest that perturbations caused by hydrodynamic interactions -- similar to what happens when the wake from a large boat affects smaller boats on a lake -- may be the most important factor in this intracellular diffusion. \u003C\/p\u003E\u003Cp\u003EA detailed understanding of the interactions inside cells -- where macromolecules can occupy as much as 40 percent of the available space -- could provide important information to the developers of therapeutic drugs and lead to a better understanding of how disease states develop. Ultimately, researchers hope to have a complete simulation of these cellular processes to help them understand a range of biological issues, from metabolism to cell division. \u003C\/p\u003E\u003Cp\u003ESponsored by the National Institutes of Health, the research was reported Oct. 11 in the early online edition of the journal \u003Cem\u003EProceedings of the National Academy of Sciences\u003C\/em\u003E. \u003C\/p\u003E\u003Cp\u003E\u0022We found that hydrodynamics -- perturbation of the solvent with eddies and wakes created by molecules in this crowded environment -- may be the dominant effect in intermolecular dynamics within cells,\u0022 said Jeffrey Skolnick, director of the Center for the Study of Systems Biology at Georgia Tech. \u0022The correlations created between molecules through this process have a lot of functional consequences for how collections of these molecules interact.\u0022 \u003C\/p\u003E\u003Cp\u003EThe motion of macromolecules within cells is normally random, occurring through Brownian motion that causes the molecules to diffuse through the cellular cytoplasm, which has viscosity similar to that of water. Researchers have studied the movement of fluorescent protein molecules injected into \u003Cem\u003EE. coli \u003C\/em\u003Ecells, but don\u2019t yet understand the forces affecting that motion. However, the measurements show that the fluorescent molecules move about 15 times more slowly inside the cell than they do in a test tube. \u003C\/p\u003E\u003Cp\u003EUsing simulations that allowed them to adjust the impacts of natural forces, Skolnick and collaborator Tadashi Ando analyzed the activity of 15 different molecules in a portion -- just one one-thousandth -- of an E. coli cell. By altering those simulated forces in the computer, they attempted to determine what may cause the reduction in diffusion speed. \u003C\/p\u003E\u003Cp\u003EThe most logical reason for that slowed movement is the crowded nature of cells, but Skolnick and Ando found that bumping into other molecules accounted for only a portion of the reduced molecular diffusion. \u003C\/p\u003E\u003Cp\u003E\u0022If you are in a crowded room and want to walk to the bar, the other people slow you down,\u0022 explained Skolnick, who is Georgia Research Alliance eminent scholar in computational systems biology. \u0022In biological processes, if there are a lot of large molecules in the way, these protein molecules can\u0027t move as quickly. But our model showed that this crowding accounted for only about a third of the reduction measured experimentally.\u0022 \u003C\/p\u003E\u003Cp\u003EThe researchers also studied the hydrodynamic forces exerted by molecules on one another. These forces are comparable to the way in which the wake of a large boat on a lake affects smaller boats, or how a swimming whale might effect a school of small fish. The interaction causes correlated motion, which was known to be important in the movement of polymers and colloids studied earlier by chemists. \u003C\/p\u003E\u003Cp\u003EBy turning off the other forces at work in their silicon world, the Georgia Tech researchers found that this correlated motion accounted for much more of the diffusion reduction than did the crowding. \u003C\/p\u003E\u003Cp\u003E\u0022The hydrodynamic interactions create cooperative motion between the molecules,\u0022 Skolnick explained. \u0022We see long-lived correlations between the molecules, independent of size, in space and time. This suggests that these correlated motions may be extremely important in the dynamics of molecules.\u0022 \u003C\/p\u003E\u003Cp\u003EThe researchers also studied other possible causes for the slow-down but found that repulsion between molecules, variations in molecular shape and \u0022stickiness\u0022 between molecules could not account for the dramatic reduction in diffusion rate. \u003C\/p\u003E\u003Cp\u003EThough the findings are interesting in themselves, their real importance may be in setting the stage for larger studies that would include the thousands of molecules known to be important to cellular operations. Researchers ultimately hope to model everything happening in the cell, including interactions with the cell membrane. \u003C\/p\u003E\u003Cp\u003E\u0022This is the beginning of what will be a very complicated effort to develop the tools and approaches that will allow us to simulate a sufficiently useful caricature of a cell,\u0022 Skolnick said. \u0022From that, we will be able to learn the biological principles at work, and then study some \u0027what if\u0027 scenarios.\u0022 \u003C\/p\u003E\u003Cp\u003EThose \u0022what if\u0022 questions might one day help drug designers better understand how therapeutic compounds work within cells, for instance, or allow cancer researchers to see how cells change from a healthy state to a disease state. \u003C\/p\u003E\u003Cp\u003E\u0022It would be great if we could study new drugs in a model set of cells to very quickly see what might be the side-effects and cross interactions to understand how we might minimize these problems,\u0022 Skolnick noted. \u0022The nice thing about a computer simulation is that if it is a reasonably faithful caricature, you can ask a lot of questions -- and get answers that help you understand what\u2019s going on.\u0022 \u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EResearch News \u0026amp; Publications Office\u003Cbr \/\u003EGeorgia Institute of Technology\u003Cbr \/\u003E75 Fifth Street, N.W., Suite 314\u003Cbr \/\u003EAtlanta, Georgia 30308 USA\u003C\/strong\u003E \u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EMedia Relations Assistance\u003C\/strong\u003E: John Toon (404-894-6986)(\u003Ca href=\u0022mailto:jtoon@gatech.edu\u0022\u003Ejtoon@gatech.edu\u003C\/a\u003E) or Abby Vogel Robinson (404-385-3364)(\u003Ca href=\u0022mailto:abby@innovate.gatech.edu\u0022\u003Eabby@innovate.gatech.edu\u003C\/a\u003E). \u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ETechnical Contact\u003C\/strong\u003E: Jeffrey Skolnick (404-407-8975)(\u003Ca href=\u0022mailto:skolnick@gatech.edu\u0022\u003Eskolnick@gatech.edu\u003C\/a\u003E). \u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EWriter\u003C\/strong\u003E: John Toon \u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"\u003Cp\u003EUsing large-scale computer simulations, researchers at the Georgia Institute of Technology have identified the most important factors affecting how molecules move through the crowded environment inside living cells.\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"A new study shows how molecules diffuse through cells."}],"uid":"27303","created_gmt":"2010-10-12 00:00:00","changed_gmt":"2016-10-08 03:07:31","author":"John Toon","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2010-10-12T00:00:00-04:00","iso_date":"2010-10-12T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"hg_media":{"62096":{"id":"62096","type":"image","title":"Movement of molecules in cells","body":null,"created":"1449176337","gmt_created":"2015-12-03 20:58:57","changed":"1475894536","gmt_changed":"2016-10-08 02:42:16","alt":"Movement of molecules in cells","file":{"fid":"191391","name":"thl04388.jpg","image_path":"\/sites\/default\/files\/images\/thl04388_0.jpg","image_full_path":"http:\/\/www.tlwarc.hg.gatech.edu\/\/sites\/default\/files\/images\/thl04388_0.jpg","mime":"image\/jpeg","size":419089,"path_740":"http:\/\/www.tlwarc.hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/thl04388_0.jpg?itok=w-Aq8uhO"}},"62097":{"id":"62097","type":"image","title":"Prof. Jeffrey Skolnick","body":null,"created":"1449176337","gmt_created":"2015-12-03 20:58:57","changed":"1475894536","gmt_changed":"2016-10-08 02:42:16","alt":"Prof. Jeffrey Skolnick","file":{"fid":"191392","name":"tvw04388.jpg","image_path":"\/sites\/default\/files\/images\/tvw04388_0.jpg","image_full_path":"http:\/\/www.tlwarc.hg.gatech.edu\/\/sites\/default\/files\/images\/tvw04388_0.jpg","mime":"image\/jpeg","size":774484,"path_740":"http:\/\/www.tlwarc.hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/tvw04388_0.jpg?itok=n7f7TOru"}}},"media_ids":["62096","62097"],"related_links":[{"url":"http:\/\/cssb.biology.gatech.edu\/","title":"Center for the Study of Sytems Biology"},{"url":"http:\/\/www.biology.gatech.edu\/","title":"School of Biology"},{"url":"http:\/\/cssb.biology.gatech.edu\/skolnick\/people\/jeff.html","title":"Jeffrey Skolnick"},{"url":"http:\/\/cssb.biology.gatech.edu\/cell_simulation","title":"Videos of simulations"},{"url":"http:\/\/www.gra.org\/","title":"Georgia Research Alliance"}],"groups":[{"id":"1188","name":"Research Horizons"}],"categories":[{"id":"140","name":"Cancer Research"},{"id":"146","name":"Life Sciences and Biology"},{"id":"149","name":"Nanotechnology and Nanoscience"},{"id":"135","name":"Research"}],"keywords":[{"id":"532","name":"cell"},{"id":"10931","name":"diffusion"},{"id":"5926","name":"Molecules"},{"id":"1107","name":"motion"}],"core_research_areas":[],"news_room_topics":[],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003E\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\u003C\/p\u003E","format":"limited_html"}],"email":["jtoon@gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}