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

微观尺度运输是肠道生理和功能中分子尺度吸收和宏观尺度混合之间的关键环节

• 批准号: 0506215
• 负责人: James Brasseur
• 金额: $ 60万
• 依托单位: Pennsylvania State Univ University Park
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0506215&HistoricalAwards=false
• 关键词: Micro; scale; Transport; Critical; Link

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.

提案编号：0506215主要制造商：J. Brasseur机构名称：宾夕法尼亚州立大学肠道生理学和功能中作为分子尺度吸收和宏观尺度混合之间的关键环节的微观尺度转运小肠的消化和药物功效取决于起源于穿过粘膜上皮的整体流动的分子的转运，以及将分泌的分子输送到具有1- 2cm尺度的宏观混合的整体流。 吸收和分泌受分子扩散到/来自覆盖肠粘膜的大量指状突起或“绒毛”（规模约100-500微米）的上皮细胞的速率限制。 反过来，上皮细胞排列着直接参与吸收的“微绒毛”（规模约为1微米）。因此，消化过程依赖于跨越几个数量级的高度耦合的多尺度传输和混合过程。 该研究将重点关注吸收和分泌的细节和神经生理学控制，通过系统模型整合从宏观混合到分子吸收的整个尺度范围，以绒毛诱导的微运输为中心，将其作为吸收的关键环节。耦合宏观到微观模型将与动物实验相结合，其中微线圈磁共振成像（MRI）将用于量化体内时空粘膜和绒毛运动。 PI将开发一种新的算法，耦合双尺度格子玻尔兹曼（LB），分子动力学（MD）和移动边界。 建模与实验的协调可以产生以前从未发现的关键知识。 这是一种分析医学上重要的生理系统（肠道吸收）的独特方法。研究领域对医学科学和临床实践的重要性怎么说都不过分。许多重大疾病与胃肠道有关，其中大多数通过吸收和/或分泌的改变影响消化。从科学角度来看，该计划有可能开辟一个新的潜在重要研究领域，对基础生理学，疾病，临床评估和治疗产生影响。 该研究团队包括具有建模，实验和MRI技术专业知识的生物工程师，GI细胞和分子神经生理学家，LB专家和临床科学家之间的新合作。 研究生和本科生将在非常不同的学科领域（生理学，力学和医学）和跨方法（建模，实验和IT）的高度跨学科课程中接受培训。通过这个项目，PI将培训生理学和医学工程师，以及生理学家和临床科学家的工程原理。一个特别的重点将是本科生，PI的目标是激发优秀的学生继续接受更高层次的教育，同时在新的跨学科方向移动。 将招募代表性不足的群体的成员，以特别鼓励他们参与最高水平的跨学科教育、科学分析和技术进步。