Systems Biophysics: Multiscale Biophysical Modeling of Organ Systems.
Systems Biophysics: Multiscale Biophysical Modeling of Organ Systems.
复制标题
系统生物物理学：器官系统的多尺度生物物理建模。
DOI：
10.1016/j.bpj.2016.02.007
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发表时间：
2016
影响因子：
3.4
通讯作者：
McCulloch,AndrewD
中科院分区：
文献类型：
--
作者：
McCulloch,AndrewD
二十世纪生物科学的还原论运动成功地利用生物化学、分子生物学和结构生物学的工具，为我们提供了越来越详细的生命系统部件清单。随着分子数据宝藏的增长，生物信息学的出现带来了信息技术，使生物科学家能够相对轻松地注释、查询、搜索和整合这些数据。这就催生了系统生物学，它致力于重建分子相互作用的网络，从而产生细胞的基本生化、生物物理和调节功能，并赋予不同细胞类型构建专门的器官系统（如中枢神经系统、肌肉骨骼系统和心血管系统）所需的独特特性。随着这些日益详细但仍然不完整的分子网络重建，为所有尺度的生物功能系统模型奠定了基础，这些模型模拟了生命系统（特别是细胞）的动态生理学，作为功能相互作用的大型电路图。这些新的定量、计算机驱动的方法具有巨大的前景，可以提供新水平的综合科学见解，并确定有前途的新药理疗法。生物系统结构精巧，关键依赖其动态三维组织来实现其生理功能。建立从分子到细胞到器官系统和有机体的生物组织物理尺度的结构整合模型的挑战是现代生物物理学的一个决定性问题。与系统生物学一样，这个多尺度建模领域是数据密集型的。我们依靠结构生物学、显微镜和医学成像技术来构建有关分子、细胞、组织和器官结构的高质量、高分辨率的数据集。但多尺度建模也很大程度上依赖于物理学来定义和限制分子和细胞过程扩展以产生组织和器官尺度生理学的方式。
The reductionist movement of twentieth century biological science successfully used the tools of biochemistry, molecular biology, and structural biology to provide us with an increasingly detailed parts list of living systems. As the troves of molecular data grew, the advent of bioinformatics brought to bear information technologies that allowed biological scientists to annotate, query, search, and integrate these data with relative ease. This gave birth to systems biology, which seeks to reconstruct networks of the molecular interactions that give rise to the essential biochemical, biophysical, and regulatory functions of cells, and that give the different cell types the unique properties they need to build specialized organ systems such as the central nervous system, the musculoskeletal system, and the cardiovascular system. With these increasingly detailed, yet invariably still incomplete, molecular network reconstructions, the foundation has been laid for systems models of biological functions at all scales that simulate the dynamic physiology of living systems, especially cells, as large circuit diagrams of functional interactions. Great promise is held by these new quantitative, computer-driven approaches that can provide a new level of integrative scientific insight and identify promising new pharmacologic therapies.Biological systems are exquisitely structured and depend critically on their dynamic three-dimensional organization to achieve their physiological functions. The challenge of building models that integrate structurally across physical scales of biological organization from molecule to cell to organ system and organism is a defining problem of modern biophysics. Like systems biology, this field of multiscale modeling is data-intensive. We depend on structural biology, microscopy, and medical imaging technologies to build high-quality, high-resolution data sets on molecular, cellular, tissue, and organ structures. But multiscale modeling also relies heavily on physics to define and constrain that ways that molecular and cellular processes can scale up to produce tissue and organ-scale physiology.