Molecular BioSystems

doi: 10.1039/c003818kpmid: N/A

doi: 10.1039/c003819apmid: N/A

doi: 10.1039/c003820mpmid: N/A

Ma, Tao; Tan, Conge; Zhang, Hui; Wang, Miqu; Ding, Weijun; Li, Shao

doi: 10.1039/b914024gpmid: 20237638

Systems biology is a general trend of contemporary scientific development. When coupling the classical traditional Chinese medicine (TCM) Cold Syndrome and methodology of systems biology, we conformed to the genome, transcriptome, proteome, and metabolome that are supposed to run through the overall macro behavior, and explored the macro and micro framework of systems biology of TCM Syndrome. We introduced a new way to probe into the implicit stratification of Cold Syndrome, after surveying 4575 cases of Cold Syndrome patients and examining gene expression information of a typical Cold Syndrome pedigree by microarray. We underlined the genetic background of the Cold Syndrome family based on the molecular foundation to understand Syndrome, one of our earlier discoveries in which genes and chemical compounds in neuro-endocrine-immune (NEI) system are scored as Cold or Hot (or both) property. Results indicate that Cold Syndrome related genes play an essential role in energy metabolism, which are tightly correlated with the genes of neurotransmitters, hormones and cytokines in the NEI interaction network. Therefore, NEI interaction not only opens out mechanism of classical TCM theory on Syndrome but also enriches current research on complex diseases as well as systems biology.

Bechtluft, Philipp; Nouwen, Nico; Tans, Sander J.; Driessen, Arnold J. M.

doi: 10.1039/b915435cpmid: 20237639

SecB is a molecular chaperone in Gram-negative bacteria dedicated to the post-translational translocation of proteins across the cytoplasmic membrane. The entire surface of this chaperone is used for both of its native functions in protein targeting and unfolding. Single molecule studies revealed how SecB affects the folding pathway of proteins and how it prevents the tertiary structure formation and aggregation to support protein translocation.

Sawant, Rupa; Torchilin, Vladimir

doi: 10.1039/b916297fpmid: 20237640

Cell penetrating peptides (CPPs), TATp, in particular, has been used widely for intracellular delivery of various agents ranging from small molecules to proteins, peptides, range of pharmaceutical nanocarriers and imaging agents. This review highlights the mechanisms of CPP-mediated delivery and summarizes numerous examples illustrating the potential of CPPs in the fields of biology and medicine.

Pierre, Sandra; Scholich, Klaus

doi: 10.1039/b910653gpmid: 20237641

The function of a protein is determined on several levels including the genome, transcriptome, proteome, and the recently introduced toponome. The toponome describes the topology of all proteins, protein complexes and protein networks which constitute and influence the microenvironment of a given protein. It has long been known that cellular function or dysfunction of proteins strongly depends on their microenvironment and even small changes in protein arrangements can dramatically alter their activity/function. Thus, deciphering the topology of the multi-dimensional networks which control normal and disease-related pathways will give a better understanding of the mechanisms underlying disease development. While various powerful proteomic tools allow simultaneous quantification of proteins, only a limited number of techniques are available to visualize protein networks in intact cells and tissues. This review discusses a novel approach to map and decipher functional molecular networks of proteins in intact cells or tissues. Multi-epitope-ligand-cartography (MELC) is an imaging technology that identifies and quantifies protein networks at the subcellular level of morphologically-intact specimens. This immunohistochemistry-based method allows serial visualization and biomathematical analysis of up to 100 cellular components using fluorescence-labelled tags. The resulting toponome maps, simultaneously ranging from the subcellular to the supracellular scale, have the potential to provide the basis for a mathematical description of the dynamic topology of protein networks, and will complement current proteomic data to enhance the understanding of physiological and pathophysiological cell functions.

Binamé, Fabien; Pawlak, Geraldine; Roux, Pierre; Hibner, Urszula

doi: 10.1039/b915591kpmid: 20237642

Movement of individual cells and of cellular cohorts, chains or sheets requires physical forces that are established through interactions of cells with their environment. In vivo, migration occurs extensively during embryonic development and in adults during wound healing and tumorigenesis. In order to identify the molecular events involved in cell movement, in vitro systems have been developed. These have contributed to the definition of a number of molecular pathways put into play in the course of migratory behaviours, such as mesenchymal and amoeboid movement. More recently, our knowledge of migratory modes has been enriched by analyses of cells exploring and moving through three-dimensional (3D) matrices. While the cells’ morphologies differ in 2D and 3D environments, the basic mechanisms that put a cellular body into motion are remarkably similar. Thus, in both 2D and 3D, the polarity of the migrating cell is initially defined by a specific subcellular localization of signalling molecules and components of molecular machines required for motion. While the polarization can be initiated either in response to extracellular signalling or be a chance occurrence, it is reinforced and sustained by positive feedback loops of signalling molecules. Second, adhesion to a substratum is necessary to generate forces that will propel the cell engaged in either mesenchymal or ameboid migration. For collective cell movement, intercellular coordination constitutes an additional requirement: a cell cohort remains stationary if individual cells pull in opposite directions. Finally, the availability of space to move into is a general requirement to set cells into motion. Lack of free space is probably the main obstacle for migration of most healthy cells in an adult multicellular organism. Thus, the requirements for cell movement are both intrinsic to the cell, involving coordinated signalling and interactions with molecular machines, and extrinsic, imposed by the physicochemical nature of the environment. In particular, the geometry and stiffness of the support act on a range of signalling pathways that induce specific cell migratory responses. These issues are discussed in the present review in the context of published work and our own data on collective migration of hepatocyte cohorts.

Muskhelishvili, Georgi; Sobetzko, Patrick; Geertz, Marcel; Berger, Michael

doi: 10.1039/b909192kpmid: 20237643

Recent advances of systemic approaches to gene expression and cellular metabolism provide unforeseen opportunities for relating and integrating extensive datasets describing the transcriptional regulation system as a whole. However, due to the multifaceted nature of the phenomenon, these datasets often contain logically distinct types of information determined by underlying approach and adopted methodology of data analysis. Consequently, to integrate the datasets comprising information on the states of chromatin structure, transcriptional regulatory network and cellular metabolism, a novel methodology enabling interconversion of logically distinct types of information is required. Here we provide a holistic conceptual framework for analysis of global transcriptional regulation as a system coordinated by structural coupling between the transcription machinery and DNA topology, acting as interdependent sensors and determinants of metabolic functions. In this operationally closed system any transition in physiological state represents an emergent property determined by shifts in structural coupling, whereas genetic regulation acts as a genuine device converting one logical type of information into the other.

Abe, Ryota; Caaveiro, Jose M. M.; Kudou, Motonori; Tsumoto, Kouhei

doi: 10.1039/b925791hpmid: 20237644

N-Acylamino acids are a new family of versatile biological surfactants capable of extracting integral membrane proteins of various topologies from the biological membrane, in many instances surpassing the efficiency of commercial detergents.