Micro-scale Transport as a Critical Link between Molecular-scale Absorption and Macro-scale Mixing in Gut Physiology and Function

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PROPOSAL NO.: 0506215PRINCIPAL INVESTIGATOR: J. BrasseurINSTITUTION NAME: Pennsylvania State UniversityMICRO-SCALE TRANSPORT AS A CRITICAL LINK BETWEEN MOLECULAR-SCALE ABSORPTION AND MACRO-SCALE MIXING IN GUT PHYSIOLOGY AND FUNCTIONDigestion and pharmaceutical efficacy of the small bowels depends on the transport of molecules originating in the bulk flow across the mucosal epithelium, and the transport of secreted molecules to the bulk flow with macro mixing at the 1-2 cm scale. Absorption and secretion are rate-limited by diffusion of molecules to/from epithelial cells covering multitudes of finger-like protuberances, or "villi" (approximately 100-500 microns in scale) that line the gut mucosa. The epithelial cells are, in turn, lined with "microvilli" (on the order of 1 micron in scale) directly involved in absorption. The process of digestion therefore relies on highly coupled multi-scale transport and mixing processes that span several orders of magnitude. The research will focus on the details and neurophysiological controls of absorption and secretion through systems models that integrate the entire range of scales from macro-mixing to molecular absorption, centering on villi-induced micro-transport as a critical link to absorption. Coupled macro- to micro- models will be integrated with animal experiments in which micro-coil magnetic resonance imaging (MRI) will be used to quantify space-time mucosal and villi motion in vivo. The PI's will develop a new class of algorithms that couple dual-scale lattice-Boltzmann (LB), molecular dynamics (MD) and moving boundaries. The coordination of modeling with experiment can yield critical knowledge never before uncovered. This is a unique approach to analyze a medically important physiological system (gut absorption). The importance of the area of research to medical science and clinical practice cannot be over stated. Many major diseases are associated with the GI tract, and most of these affect digestion through alterations in absorption and/or secretion. Scientifically, this program has the potential to open a new area of potentially important research with implications to basic physiology, disease, clinical evaluation, and treatment. The research team includes new collaborations among bioengineers with expertise in modeling, experiment, and MRI technology, a GI cellular and molecular neurophysiologist, an LB expert, and a clinical scientist. Graduate and undergraduate students will be trained in a highly interdisciplinary program both across very different subject areas (physiology, mechanics, and medicine) and across methodologies (modeling, experiment, and IT). Through this program The PI's will train engineers in physiology and medicine, and physiologists and clinical scientists in the principles of engineering. A particular focus will be on the undergraduate students where the PI's aim to excite exceptional students to go on to higher levels of education while moving in new interdisciplinary directions. Members of underrepresented groups will be recruited in order to provide particular encouragement for their involvement in the highest levels of interdisciplinary education, scientific analysis, and advances in technology.