NS  Vol.2 No.3 , March 2010
Protein phase instability developed in plasma of sick patients: clinical observations and model experiments
Abstract: This article discusses the causes of formation of micron-size protein structures in liquid plasma or serum of the patients with different diseases, which are accompanied by inflammatory reac-tions. Self-organizing processes in sessile dry-ing drops of natural and model biological liq-uids are used for study of possible mechanisms of development the protein phase instability in serum. There was shown that violation of opti-mal ratio between albumin and osmotic active components could lead to loss of albumin ag-gregative stability and albumin coagulation structures formation. Possible role of these structures in pathogenesis of inflammation is discussed.
Cite this paper: Yakhno, T. (2010) Protein phase instability developed in plasma of sick patients: clinical observations and model experiments. Natural Science, 2, 220-227. doi: 10.4236/ns.2010.23034.

[1]   Yakhno, T.A., Sedova, O.A., Sanin, A.G. and Pelyushenko, A.S. (2003) On the existence of regular structures in the liquid human blood serum (plasma) and phase transitions in the course of its drying. Technical Physics, 48(4), 399-403.

[2]   Yakhno, T. (2008) Salt-induced protein phase transitions in drying drops. Journal of Colloid and Interface Science ,318, 225-230.

[3]   Velev, O.D., Kaler, E.W. and Lenhoff, A.M. (1998) Protein interactions in solution characterized by light and neutron scattering: comparison of lysozyme and chymotrip- sinogen. Biophysical Journal, 75, 2682-2697.

[4]   Thomson, J.A., Schurtenberger, P., Thurston, G.M. and Benedek, G.B. (1987) Binary liquid phase separation and critical phenomena in protein/water solution, Proceedings of the National Academy of Sciences, USA, 84, 7079-7083.

[5]   Kaibara, K., Okazaki, T., Bohidar, H.B. and Dubin, P.L. (2000) pH-induced coacervation in complexes of bovine serum albumin and cationic polyelectrolytes, Biomac- romolecules, 1,100-107.

[6]   Seyrek, E., Dubin, P.L., Tribet, C. and Gamble, E.A. (2003) Ionic strength dependence of protein-polyelectrolyte interactions. Biomacromolecules, 4, 273-282.

[7]   Wang, Y., Kimura, K., Huang, Q., Jaeger, W. and Dubin, P.L. (1999) Effects of salt on polyelectrolyte-micelle coacervation. Macromolecules, 32, 7128-7134.

[8]   Tanaka, S., Yamamoto, M., Ito, K., Hayakawa, R., Ataka, M. (1997) Relation between the phase separation and the crystallization in protein solutions. Physical Review E, 56(1), R67-R69.

[9]   Chang, B.H. and Bae, Y.C. (2003) Salting-out in the aqueous single-protein solution: the effect of shape factor. Biophysical Chemistry, 104, 523-533.

[10]   Fulton, A.B. (1982) How crowded is the cytoplasm? Cell, 30(2), 345–347.

[11]   Ellis, R.J. and Minton, A.P. (2006) Protein aggregation in crowded environments. Journal of Biological Chemistry, 387, 485-497.

[12]   [12]Zimmerman, S.B. and Trach, S.O. (1991) Estimation of macromolecule concentrations and excluded volume effects for the cytoplasm of Escherichia Coli. Journal of Molecular Biology, 222, 599-620.

[13]   Vazquez, A., Beg, Q.K., Demenezes, M.A. and Ernst, J., Bar-Joseph, Z., Barabasi, A.L., Boros, L.G., Oltavi, Z.N. (2008) Impact of the solvent capacity constraint on E. Coli metabolism. BMC Systems Biology, 2, 7-10.

[14]   Mattison, K.W., Dubin, P.L. and Brittain, I.J. (1998) Complex formation between bovine serum albumin and strong polyelectrolytes: Effect of polymer charge density. Journal of Physical Chemistry B, 102, 3830-3836.

[15]   Azegami, S, Tsuboi, A., Izumi, T., Hirata, M., Dubin, P. L., Wang, B. and Kokufuta, E. (1999) Fotmation of an intrapolymer complex from human serum albumin and poly(ethylene glycol). Langmuir, 15, 940-947.

[16]   Tripp, B.C., Magda, J. J. and Andrade, J.D. (1995) Adsorption of globular proteins at the air/water interface, as measured via dynamic surface tension. Concentration dependence, mass-transfer considerations, and adsorption kinetics. Journal of Colloid and Interface Science, 173, 16-27.

[17]   Pande A., Pande, J., Asherie, N., Lomakin, A., Ogun, O., King, J.A., Lubsen, N.H., Walton, D. and Benedek, G.B. (2000) Molecular basis of a progressive juvenile-onset hereditary cataract. Proceedings of the National Academy of Sciences, 97(5), 1993-1998.

[18]   Simpanya, M.F., Ansari, R.R., Suh, K.I., Leverenz, V.R. and Giblin, G.J. (2005) Aggregation of lens crystallins in an in vivo hyperbaric oxygen Guinea pig model of nuclear cataract: dynamic light-scattering and HPLC analysis. Investigative Ophthalmology & Visual Science, 46, 4642-4651.

[19]   Stradner, A., Foffi, G., Dorsaz, N., Thurston, G. and Schurtenberger, P. (2007) New Insight into cataract formation: Enhanced stability through mutual attraction. Physical Review Letters, 99, 198103.

[20]   Green, M.A., Noguchi, C.T., Keydan, A.J., Marwah, S.S. and Stuart, J. (1998) Polymerization of sickle cell hem- oglobin at arterial oxygen saturation impairs erythrocyte deformability. Journal of Clinical Investigation, 81, 1669-1674.

[21]   Ahn, S.-M., Byun, K., Cho, K., Kim, J. Y., Yoo, J. S., Kim, D., Paek, S. H., Kim, S. U., Simpson, R. J. and Lee, B. (2008) Human microglial cells synthesize albumin in brain. Plos ONE, 3(7), e2829.

[22]   Yakhno, T.A., Yakhno, V.G., Sanin, A.G., Sanina, O.A. and Pelyushenko, A.S. (2003) A Method for Liquid Analysis by means of Phase Transitions during drop drying. Proceedings of SPIE, Bioengineered and Bio- inspired Systems, 19-21 May, Maspolamas, Gran Canaria, Spain, 5119, 87-99.

[23]   Yakhno, T., Sanin, A., Yakhno, V., Pelyushenko, A., Egorova, N.A., Terentiev, I.G., Smetanina, S.V., Korochkina, O.V. and Yashukova, E.V. (2005) The informative-capacity phenomenon of drying drops. Aptitude test in medical diagnostics. IEEE Engineering in Medicine and Biology Society, 24, 2, 96-104.

[24]   Yakhno, T., Sanin, A., Pelyushenko, A., Kazakov, V., Shaposhnikova, O., Chernov, A., Yakhno, V., Vacca, C., Falcone, F. and Johnson, B. (2007) Uncoated quartz resonator as a universal biosensor. Biosensors and Bioelectronics, 22, 9-10, 2127-2131.

[25]   Yakhno, T.A., Kazakov, V.V., Sanin, A.G., Shapo- shnikova, O.B. and Chernov, A.S. (2007) Dynamics of Phase Transitions in Drying Drops of Human Serum Protein Solutions. Technical Physics, 52(4), 515–520.

[26]   Yakhno, T.A., Kazakov, V.V., Sanin, A.G., Shapo- shnikova, O.B. and Chernov, A.S. (2007) Mechanical Properties of Adsorption Layers in Solutions of Human Blood Serum Proteins: A Comparative Assessment. Technical Physics, 52(4), 510–514.

[27]   Heil, W., Koberstein, R. and Zawta, B. (2001) Reference Ranges for Adults and Children: Pre-Analytical Con- siderations. Boehringer, Mannheim, 1997, Labpress, 176, Moscow.

[28]   Ben-Ami, R., Barshtein, G, Mardi, T., Deutch, V., Elkayam, O. and Berliner, S. (2003) A synergistic effect of albumin and fibrinogen on immunoglobulin-induced red blood cell aggregation. American Journal of Physiology, Heart and Circulatory Physiology, 285, H2663-H2669.

[29]   Shacter, E., Arzadon, G.K. and Williams, J.A. (1993) Stimulation of interleukin-6 and prostaglandin E2 secretion from peritoneal macrophages by polymers of albumin. Blood, 82, 2853-2864.

[30]   Deegan, R.D. (2000) Pattern formation in drying drops. Physical Review E, 61(1), 475-485.

[31]   Popov, Y. (2005) Evaporative deposition patterns: Spatial dimensions of the deposit. Physical Review Letters, 71, 036313.

[32]   Yakhno, T. and Yakhno, V. (2009) Structural evolution of drying drops of biological fluids. Technical Physics, 54(8), 1219-1227.

[33]   Ling, G.N. (2000) Life at the cell and bellow-cell level. The hidden history of a fundamental revolution in biology. Pacific Press, 280. Also available: http://biopa

[34]   Pollak, G.H. (2001) Cells, gels and the engines of life. Ebner & Sons, Seattle, 301. WA, USA.

[35]   Cooper, C.L., Dubin, P.L., Kayitmazer, A.B., Turksen, S. (2005) Polyelectrolyte-protein complexes. Current Op- inion in Colloid and Interface Science, 10, 52-78.

[36]   Peters, T. (1996) All about albumin: Biochemistry, genetics, and medical applications. San Diego, Academic press.

[37]   Petricoin, E.F., Belluco, C., Araujo, R.P., Liotta, L.A. (2006) The blood peptidome: A higher dimension of information content for cancer biomarker discovery. Nature Reviews Cancer, 6, 961-967.

[38]   Quinlan, G.J., Martin, G.S., Evans, T.W. 2005. Albumin: Biochemical properties and potential. Hepathology, 41, 1211-1219.

[39]   Keyser, J.W. (1995) Standardization of dye-binding methods for estimation of serum albumin. Clinica Chimica Acta, 11, 477-9.

[40]   Blaaberg, O. and Hylton, P.P. (1979) Effect of aggregates on albumin standardization. Scandinavian Journal of Clinical and Laboratory Investigation, 39, 751-7.

[41]   Bormer, O.P., Amlie, L.M., Paus, E. and Kongsgard, U. (1999) Automated albumin method underestimates phar- maceutical-grade albumin in vivo. Clinical Chemistry, 45(7), 1082-1084.

[42]   Reviewers, C.I.G.A. (1998) Human albumin administration in critically ill patients: Systematic review of randomised controlled trials. British Medical Journal, 317, 235-240.

[43]   Pulimood, T.B. and Park, G.R. (2000) Debate: Albumin administration should be avoided in the critically ill. Critical Care, 4, 151-155. Also available: http://ccforum/ content/4/3/151

[44]   Forsdyke, D.R., Palfree, R.G.E. and Takeda, A. (1982) Formation of erythrocyte rouleaux in preheated normal serum: roles of albumin polymers and lysophosp- hatidylcholine. Canadian Journal of Biochemistry, 60(7), 705-711.

[45]   Candilores, H., Muller, S., Ziegler, O., Donner, M. and Drouin, P. (1996) Role of albumin glycation on the erythrocyte aggregation: An in vitro study. Diabetic Medicine, 13(7), 646-650.

[46]   Reinke, W., Gaehtgens, P. and Johnson, P.C. (1987) Blood viscosity in small tubes: effect of shear rate, aggregation, and sedimentation. American Journal of Physiology, 253(3), H540-547.

[47]   Armstrong, J.K., Wenby, R.B., Meiselman, H.J. and Fisher, T.C. (2004) The hydrodynamic radii of mac- romolecules and their effect on red blood cell aggregation. Biophysical Journal, 87, 4259-4270.

[48]   Deegan, R.D., Bakajin, O., Dupont, T.F., Huber, G., Nagel, S.R., Witten, T.A. (2000) Contact line deposits in an evaporating drop. Physical Review E, 62(1), 756-776.