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The Differential Response of Proteins to Macromolecular Crowding

Michela Candotti, Modesto Orozco, Alexander MacKerell
2016 PLoS Computational Biology  
The habitat in which proteins exert their function contains up to 400 g/L of macromolecules, most of which are proteins.  ...  Instead, the impact of protein crowding on the structure and dynamics of a protein depends on its degree of disorder and results from two competing effects: the excluded volume, which favors compact states  ...  For NCBD, the values of all three conformations (three folded and three unfolded) are grouped. doi:10.1371/journal.pcbi.1005040.g003 The Response of Proteins to Macromolecular Crowding PLOS Computational  ... 
doi:10.1371/journal.pcbi.1005040 pmid:27471851 pmcid:PMC4966950 fatcat:jf5zxc6nlreediw44ooebbv3jq

Macromolecular Crowding Directs Extracellular Matrix Organization and Mesenchymal Stem Cell Behavior

Adam S. Zeiger, Felicia C. Loe, Ran Li, Michael Raghunath, Krystyn J. Van Vliet, Effie C. Tsilibary
2012 PLoS ONE  
Macromolecular crowding in extracellular culture media directly induced supramolecular assembly and alignment of extracellular matrix proteins deposited by cells, which in turn increased alignment of the  ...  We quantified the impact of induced crowding on the extracellular and intracellular protein organization of human mesenchymal stem cells (MSCs) via immunocytochemistry, atomic force microscopy (AFM), and  ...  Acknowledgments We would like to thank J Rodriguez for assistance in wound healing and proliferation assays, and DJ Irvine for discussion of endocytosis assays. Author Contributions  ... 
doi:10.1371/journal.pone.0037904 pmid:22649562 pmcid:PMC3359376 fatcat:2if3cffwzrasrfpn2b24np242u

Implications of macromolecular crowding for signal transduction and metabolite channeling

J. M. Rohwer, P. W. Postma, B. N. Kholodenko, H. V. Westerhoff
1998 Proceedings of the National Academy of Sciences of the United States of America  
Addition of the macromolecular crowding agents polyethylene glycol (PEG) 6000 and PEG 35000 led to a sharper decrease in the combined f lux-response coefficient, in one case to values of Ϸ1.  ...  This suggests that macromolecular crowding decreases the dissociation rate constants of enzyme complexes.  ...  J. van der Vlag and K. van Dam for helpful discussions and the following organizations for financial support: the South African Foundation for Research Development, the Harry Crossley Foundation, and The  ... 
doi:10.1073/pnas.95.18.10547 pmid:9724740 pmcid:PMC27931 fatcat:ps2tqtm26ngmpeo6cryr6rcap4

Macromolecular Crowding Facilitates Adipogenic Microenvironments for Human Mesenchymal Stem Cells

Felicia C. Loe, Krystyn Van Vliet, Michael Raghunath
2011 Biophysical Journal  
Preliminary data revealed either depolarizing or hyperpolarizing V m responses in the cells, the nature of which was determined by the relative timing of the IR pulse applications to threshold, electrically-induced  ...  To further investigate the response in adult cardiomyocytes, whole cell patch clamp measurements were performed to monitor sarcolemma membrane potential (V m ) changes during IR stimulation.  ...  We find that this maintenance of crowding more typical of in vivo environments substantially amplifies the adipogenic differentiation response, as compared to standard protocols of chemically induced differentiation  ... 
doi:10.1016/j.bpj.2010.12.3578 fatcat:hlaokregjjh4liaevjujaecfsi

Crowding and hydrodynamic interactions likely dominate in vivo macromolecular motion

T. Ando, J. Skolnick
2010 Proceedings of the National Academy of Sciences of the United States of America  
To begin to elucidate the principles of intermolecular dynamics in the crowded environment of cells, employing Brownian dynamics (BD) simulations, we examined possible mechanism(s) responsible for the  ...  Macromolecular crowding exerts surprisingly large effects on the thermodynamics and kinetics of processes such as macromolecular association, protein stability, and enzyme activity (1, 4, 5).  ...  J.S. and T.A. conceived the project, T.A. performed the algorithm development and calculations.  ... 
doi:10.1073/pnas.1011354107 pmid:20937902 pmcid:PMC2973006 fatcat:a3s4hqss6fft3m76v3qgc36ili

Phase separation in cytoplasm, due to macromolecular crowding, is the basis for microcompartmentation

Harry Walter, Donald E. Brooks
1995 FEBS Letters  
The macromolecular diversity and concentrations in the fluid phase of cytoplasm constitute conditions necessary and sufficient for aqueous phase separation.  ...  Consequences of phase separation in cytoplasm, including its 'compartmentation', are inferred from analogies with the physicochemical properties of aqueous two-phase systems and with the partitioning behavior  ...  magnified by the effects of macromolecular crowding.  ... 
doi:10.1016/0014-5793(95)00159-7 pmid:7698310 fatcat:xj5ps5mx4vcl7jdtydwgvbrx2e

Effect of PDMS Nanopatterned Substrates on Embryonic Stem Cells Differentiation into Neuronal Lineage

Elisa Migliorini, Gianluca Grenci, Jelena Ban, Alessandro Pozzato, Maria Elisabetta Ruaro, Massimo Tormen, Vincent Torre, Marco Lazzarino
2011 Biophysical Journal  
Preliminary data revealed either depolarizing or hyperpolarizing V m responses in the cells, the nature of which was determined by the relative timing of the IR pulse applications to threshold, electrically-induced  ...  To further investigate the response in adult cardiomyocytes, whole cell patch clamp measurements were performed to monitor sarcolemma membrane potential (V m ) changes during IR stimulation.  ...  We find that this maintenance of crowding more typical of in vivo environments substantially amplifies the adipogenic differentiation response, as compared to standard protocols of chemically induced differentiation  ... 
doi:10.1016/j.bpj.2010.12.3579 fatcat:5lna57gp3fdmnaelvfpd756sgm

Mechanisms Underlying Pulsed Infrared Stimulation of Cardiomyocytes

Gregory M. Dittami, Kenneth W. Spitzer, Suhrud M. Rajguru, Richard A. Lasher, Robert W. Hitchcock, Richard D. Rabbitt
2011 Biophysical Journal  
Preliminary data revealed either depolarizing or hyperpolarizing V m responses in the cells, the nature of which was determined by the relative timing of the IR pulse applications to threshold, electrically-induced  ...  To further investigate the response in adult cardiomyocytes, whole cell patch clamp measurements were performed to monitor sarcolemma membrane potential (V m ) changes during IR stimulation.  ...  We find that this maintenance of crowding more typical of in vivo environments substantially amplifies the adipogenic differentiation response, as compared to standard protocols of chemically induced differentiation  ... 
doi:10.1016/j.bpj.2010.12.3577 fatcat:tiyx3hypqbf5rmppzhmag5ajga

Interfacing Three-Dimensional Curved Structures and Cellular Adhesion

Mary E. Wilson, Nithyanand Kota, Burak O. Ozdoganlar, Yadong Wang, Donna B. Stolz, Philip R. LeDuc
2011 Biophysical Journal  
Preliminary data revealed either depolarizing or hyperpolarizing V m responses in the cells, the nature of which was determined by the relative timing of the IR pulse applications to threshold, electrically-induced  ...  To further investigate the response in adult cardiomyocytes, whole cell patch clamp measurements were performed to monitor sarcolemma membrane potential (V m ) changes during IR stimulation.  ...  We find that this maintenance of crowding more typical of in vivo environments substantially amplifies the adipogenic differentiation response, as compared to standard protocols of chemically induced differentiation  ... 
doi:10.1016/j.bpj.2010.12.3581 fatcat:3wq5hdtxoncwnpp4ugexal7xby

Wnt-Catenin Signaling System Functions in Embryoid Bodies Aggregated from Human Embryonic Stem Cell

Xuehong Xu, MengMeng Xu, Xunzhang Chen, Odell Jones, Harry Davis, Shangen Zheng, Joseph Bryant
2011 Biophysical Journal  
Preliminary data revealed either depolarizing or hyperpolarizing V m responses in the cells, the nature of which was determined by the relative timing of the IR pulse applications to threshold, electrically-induced  ...  To further investigate the response in adult cardiomyocytes, whole cell patch clamp measurements were performed to monitor sarcolemma membrane potential (V m ) changes during IR stimulation.  ...  We find that this maintenance of crowding more typical of in vivo environments substantially amplifies the adipogenic differentiation response, as compared to standard protocols of chemically induced differentiation  ... 
doi:10.1016/j.bpj.2010.12.3580 fatcat:opwx4lu55zcs7e4i5j5mvynuda

Lipid Composition and Macromolecular Crowding Effects on CYP2J2-Mediated Drug Metabolism in Nanodiscs

Hannah C. Huff, Demetri Maroutsos, Aditi Das
2019 Protein Science  
Overall, these studies are the first report on the role of the surrounding lipid environment and macromolecular crowding in modulating enzymatic function of CYP2J2-CPR membrane protein system.  ...  Lipid composition and macromolecular crowding are key external effectors of protein activity and stability whose role varies between different proteins.  ...  Acknowledgments The authors would like to thank the Sligar Lab for use of their fermenter to grow MSP for nanodiscs and Dr. Li  ... 
doi:10.1002/pro.3603 pmid:30861250 pmcid:PMC6459993 fatcat:fof7muzhcncxbjly2tprk4ou64

Macromolecular crowding and its potential impact on nuclear function

Karsten Richter, Michelle Nessling, Peter Lichter
2008 BBA - Molecular Cell Research  
The very special composition of the cell nucleus, which is packed with high-molecular chromatin, ribonucleo-particles and associated proteins, suggests that crowding-effects are part of nuclear functionality  ...  momentum for the assembly of macromolecular complexes, we here elaborate why macromolecular crowding may be functionally important in supporting the statistical significance of nuclear activities.  ...  We also greatly acknowledge the very helpful discussions on the manuscript with our colleague M. Rogers (DKFZ, Heidelberg).  ... 
doi:10.1016/j.bbamcr.2008.07.017 pmid:18723053 fatcat:eay35ogowrhsjcxckmfx4ygcni

What Macromolecular Crowding Can Do to a Protein

Irina Kuznetsova, Konstantin Turoverov, Vladimir Uversky
2014 International Journal of Molecular Sciences  
Sci. 2014, 15 23091 macromolecular crowding on a protein molecule.  ...  Studies under these conditions revealed that macromolecular crowding might affect protein structure, folding, shape, conformational stability, binding of small molecules, enzymatic activity, protein-protein  ...  Macromolecular crowding was proposed to be responsible for the enhanced tendency of soluble macromolecules to associate with membrane proteins that defines the ability of small fractional changes of cell  ... 
doi:10.3390/ijms151223090 pmid:25514413 pmcid:PMC4284756 fatcat:qj5fwpkkfzeuvh52g3uoo353em

Protein Folding Modulation in Cells Subject to Differentiation and Stress

David Gnutt, Linda Sistemich, Simon Ebbinghaus
2019 Frontiers in Molecular Biosciences  
Using MG132, a common proteasome inhibitor and inducer of the unfolded protein response, we show that changes to the quality control machinery modulate the folding equilibrium, leading to protein destabilization  ...  Our study explores the range of protein folding modulation within cells subject to differentiation or stress that must be encountered in the development of cytomimetic media.  ...  Wiese (Bochum) for providing the PC12 cells.  ... 
doi:10.3389/fmolb.2019.00038 pmid:31179287 pmcid:PMC6544126 fatcat:pmy4xfi44ngq5cgwszeywbfdkm

Cardiac Excitation-Contraction Coupling Proteins: A 3D Spatial Analysis

Evan I. Blumgart, Isuru D. Jayasinghe, Michael J. O'Sullivan, Christian Soeller, Cameron G. Walker, Vijay Rajagopal
2011 Biophysical Journal  
We find that this maintenance of crowding more typical of in vivo environments substantially amplifies the adipogenic differentiation response, as compared to standard protocols of chemically induced differentiation  ...  This work demonstrates that in vivo levels of macromolecular crowding accelerate deposition of the ECM microenvironment, and that the application of MMC ex vivo can enhance hMSC differentiation potential  ... 
doi:10.1016/j.bpj.2010.12.3576 fatcat:a44ic7k4rjef3inq3rh5iph7ka
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