NS  Vol.2 No.3 , March 2010
Protein phase instability developed in plasma of sick patients: clinical observations and model experiments
Author(s) Tatiana Yakhno
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 radigma.narod.ru/hidden_history/ling_newbook.htm

[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.