{"100581":{"#nid":"100581","#data":{"type":"news","title":"Cracking Cellular Motion","body":[{"value":"\u003Cp\u003EAmerican Scientist\u003Cbr \/\u003E\nCatherine Clabby\n\u003C\/p\u003E\n\u003Cp\u003EThree centuries after English scientist Robert Hooke first observed a cell with a microscope, multiple mysteries persist about life\u00e2\u0080\u0099s primary building blocks.\n\u003C\/p\u003E\n\u003Cp\u003EIt\u00e2\u0080\u0099s certain that cells are active places crowded with specialized biological components, including macromolecules. Those components communicate and otherwise interact to conduct the business of life. But we can\u00e2\u0080\u0099t yet explain, never mind mimic, precisely how it all works.\n\u003C\/p\u003E\n\u003Cp\u003E2011-01SciObsClabbyFA.jpgClick to Enlarge ImageNow two Georgia Institute of Technology researchers appear to have pushed the mission forward. Using advanced computer simulations, Jeffrey Skolnick and Tadashi Ando have identified hydrodynamic interactions as a key factor influencing movement\u00e2\u0080\u0022more specifically diffusion\u00e2\u0080\u0022inside cells.\n\u003C\/p\u003E\n\u003Cp\u003EWhen a molecule moves, the cellular fluid surrounding it gets disturbed. That affects the movement of other molecules, the pair concluded, just as one boat\u00e2\u0080\u0099s wake affects the motion of another craft traveling in the same lake.\n\u003C\/p\u003E\n\u003Cp\u003E\u00e2\u0080\u009cIt is exactly like a wake. If you start to move a solid through a liquid, you create a solvent flow. Imagine a very crowded day on Chesapeake Bay and all the sailboats are out. If you have ever been there you\u00e2\u0080\u0099ve seen that they interfere with one another. What\u00e2\u0080\u0099s remarkable is that these interactions persist almost to the molecular level,\u00e2\u0080\u009d says Skolnick, director of the Center for the Study of Systems Biology at Georgia Tech.\n\u003C\/p\u003E\n\u003Cp\u003ESkolnick and Ando, a postdoctoral scientist, reached this understanding after exploring a discrepancy. It has been long observed that macromolecules diffuse more slowly in native cytoplasm than they do in water, even though their viscosity is nearly the same. In at least one well-studied case, that of the molecular-laboratory workhorse green fluorescent protein (GFP), the rate in cytoplasm is ten times slower than the rate in water.\n\u003C\/p\u003E\n\u003Cp\u003EThe Georgia Tech scientists knew that proteins, nucleic acids and other macromolecules typically occupy 20 to 40 percent of cytoplasm volume. And they assumed that a physical principle played a role in the diffusion disparity there. \u00e2\u0080\u009cWe deeply believe that the principles of physics should work for biology,\u00e2\u0080\u009d Skolnick says. But they didn\u00e2\u0080\u0099t know what principle counted most.\n\u003C\/p\u003E\n\u003Cp\u003ESo they developed a simplified computer model of an E. coli cytoplasm populated by 15 different macromolecule types. Then, based on measurements of the molecules\u00e2\u0080\u0099 physical properties detailed in the scientific literature, they calculated the likely effects of multiple natural forces on those macromolecules. That included estimates of attraction and repulsion between molecules, the effect of their different shapes, and their hydrodynamic interactions. Crowding alone drops the diffusion constant of GFP by a factor of three. Then, by far, the influence of hydrodynamics\u00e2\u0080\u0022which produced size-independent intermolecular effects\u00e2\u0080\u0022was the biggest. When it was considered too, the green fluorescent protein\u00e2\u0080\u0099s diffusion constant matched the rate in vivo.\n\u003C\/p\u003E\n\u003Cp\u003EThe pair\u00e2\u0080\u0099s observation, published in October in the Proceedings of the National Academy of Sciences of the U.S.A., will be useful to other scientists trying to build dependable predictions of how proteins in cells interact, says David Thirumalai, director of the Biophysics Program in the Institute for Physical Science and Technology at the University of Maryland. Before anyone can estimate the timing of those interactions, it\u00e2\u0080\u0099s vital to know how quickly cells\u00e2\u0080\u0099 components can move, he says.\n\u003C\/p\u003E\n\u003Cp\u003E\u00e2\u0080\u009cJeff and [Tadashi] have shown that to compute this stuff, you must take into account the effects of the hydrodynamic interactions. This has been known to people doing fluid dynamics for a long time. In the context of cellular biology, this helps set time scales for biological processes,\u00e2\u0080\u009d Thirumalai says. \u00e2\u0080\u009cOne must know how to compute the diffusion constants to make the next step and predict how quickly some reactions will take place.\u00e2\u0080\u009d\n\u003C\/p\u003E\n\u003Cp\u003EFor Skolnick and Thirumalai, findings such as these also contribute to a much larger goal: the drive to more realistically simulate whole cells with computers, or \u00e2\u0080\u009cin silico.\u00e2\u0080\u009d Multiple laboratories worldwide are chasing that very thing. Skolnick for years has sought ways to predict the structure of biologically active forms of proteins. Thirumalai is hunting for general principles that govern the folding of biomolecules.\n\u003C\/p\u003E\n\u003Cp\u003EBiologists have made huge strides in recent decades in producing \u00e2\u0080\u009cthe parts list\u00e2\u0080\u009d of molecular life, Skolnick says. The challenge now is to accurately place those parts into a dynamic view of the components interacting with one another.\n\u003C\/p\u003E\n\u003Cp\u003EOnce that\u00e2\u0080\u0099s done, Skolnick says, researchers can ask lots of new questions, knowing, of course, that they are working with caricatures of real cells. Still, better understanding may be coming of the mechanics of evolution, he says, or just how normal cells transform into cancer cells, among many other things.\n\u003C\/p\u003E\n\u003Cp\u003E\u00e2\u0080\u009cYou have the possibility of looking at a lot of life,\u00e2\u0080\u009d Skolnick says.\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"American Scientist\nBy:Catherine Clabby\n\nThree centuries after English scientist Robert Hooke first observed a cell with a microscope, multiple mysteries persist about life\u00e2\u0080\u0099s primary building blocks.\n\nIt\u00e2\u0080\u0099s certain that cells are active places crowded with specialized biological components, including macromolecules. Those components communicate and otherwise interact to conduct the business of life. But we can\u00e2\u0080\u0099t yet explain, never mind mimic, precisely how it all works.","format":"limited_html"}],"field_summary_sentence":[{"value":"Cracking Cellular Motion"}],"uid":"27245","created_gmt":"2011-02-07 01:00:00","changed_gmt":"2016-10-08 03:11:09","author":"Troy Hilley","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2011-02-07T00:00:00-05:00","iso_date":"2011-02-07T00:00:00-05:00","tz":"America\/New_York"},"extras":[],"hg_media":{"100591":{"id":"100591","type":"image","title":"Skolnick","body":null,"created":"1449178159","gmt_created":"2015-12-03 21:29:19","changed":"1475894717","gmt_changed":"2016-10-08 02:45:17"}},"media_ids":["100591"],"related_links":[{"url":"http:\/\/www.americanscientist.org\/issues\/pub\/2011\/1\/cracking-cellular-motion","title":"American Scientist Article"},{"url":"http:\/\/www.biology.gatech.edu\/","title":"School of Biology"},{"url":"http:\/\/cssb.biology.gatech.edu\/","title":"Center for the Study of Sytems Biology"},{"url":"http:\/\/www.americanscientist.org\/","title":"American Scientist"}],"groups":[{"id":"1275","name":"School of Biological Sciences"}],"categories":[],"keywords":[],"core_research_areas":[],"news_room_topics":[],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cstrong\u003ESchool of Biology\u003C\/strong\u003E\u003Cbr \/\u003EBiology\u003Cbr \/\u003E\u003Ca href=\u0022mailto:admin@biology.gatech.edu\u0022\u003EContact School of Biology\u003C\/a\u003E\u003Cbr \/\u003E\u003Cstrong\u003E404-894-3700\u003C\/strong\u003E","format":"limited_html"}],"email":["admin@biology.gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}