Citation: Kazuma Yasuhara, Kenichi Kuroda. Kinetic study of all-or-none hemolysis induced by cationic amphiphilic polymethacrylates with antimicrobial activity[J]. Chinese Chemical Letters, ;2015, 26(4): 479-484. doi: 10.1016/j.cclet.2015.01.029 shu

Kinetic study of all-or-none hemolysis induced by cationic amphiphilic polymethacrylates with antimicrobial activity

Kazuma Yasuhara ^a,, ,
Kenichi Kuroda ^b,,

1.
a Graduate School of Materials Science, Nara Institute of Science and Technology, Ikoma, Nara 6300192, Japan;
2.
b Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI 48109, USA

Corresponding author: Kazuma Yasuhara, Kenichi Kuroda,
Received Date: 13 November 2014
Available Online: 16 January 2015
Fund Project: and JSPS KAKENHI, Grant-in-Aids for Challenging Exploratory Research (No. 25650053) for Young Scientists (Nos. 24681028 and 22700494 to KY). We thank Professor Robertson Davenport at the University of Michigan Hospital for supplying the red blood cells. We also thank Professor Edmund F. Palermo at Rensselaer Polytechnic Institute for his valuable discussions and comments. (No. DMR-0845592 to KK)

To gain an understanding of the toxicity of antimicrobial polymers to human cells, their hemolytic action was investigated using human red blood cells (RBCs). We examined the hemolysis induced by cationic amphiphilicmethacrylate random copolymers, which have amino ethyl sidechains as cationic units and either butyl or methyl methacrylate as hydrophobic units. The polymer with 30 mol% butyl sidechains (B₃₀) displayed higher hemolytic toxicity than the polymer with 59 mol% methyl sidechains (M₅₉). B₃₀ also induced faster release of hemoglobin from RBCs than M₅₉. A new theoretical model is proposed based on two consecutive steps to form active polymer species on the RBC membranes, which are associated to RBC lysis. This model takes the all-or-none release of hemoglobin by the rupture of RBCs into account, providing new insight into the polymer-induced hemolysis regarding how individual or collective cells respond to the polymers.
- Hemolysis,
- Antimicrobial polymer,
- Amphiphilic polymethacrylate,
- Kinetic analysis,
- Membrane disruption
1. [1]
  [1] H.W. Boucher, G.H. Talbot, J.S. Bradley, et al., Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America, Clin. Infect. Dis. 48 (2009) 1-12.
2. [2]
  [2] K. Kuroda, W. DeGrado, Amphiphilic polymethacrylate derivatives as antimicrobial agents, J. Am. Chem. Soc. 127 (2005) 4128-4129.
3. [3]
  [3] H. Takahashi, E.F. Palermo, K. Yasuhara, G.A. Caputo, K. Kuroda, Molecular design, structures, and activity of antimicrobial peptide-mimetic polymers, Macromol. Biosci. 13 (2013) 1285-1299.
4. [4]
  [4] K. Kuroda, G.A. Caputo, Antimicrobial polymers as synthetic mimics of hostdefense peptides, Wires Nanomed. Nanobiotechnol. 5 (2013) 49-66.
5. [5]
  [5] E.F. Palermo, S. Vemparala, K. Kuroda, Cationic spacer arm design strategy for control of antimicrobial activity and conformation of amphiphilic methacrylate random copolymers, Biomacromolecules 13 (2012) 1632-1641.
6. [6]
  [6] I. Sovadinova, E.F. Palermo, M. Urban, et al., Activity and mechanism of antimicrobial peptide-mimetic amphiphilic polymethacrylate derivatives, Polymers 3 (2011) 1512-1532.
7. [7]
  [7] W. van't Hof, E. Veerman, E.J. Helmerhorst, A. Amerongen, Antimicrobial peptides: properties and applicability, Biol. Chem. 382 (2001) 597-619.
8. [8]
  [8] G.E. Rowe, R.A. Welch, Assays of hemolytic toxins, Methods Enzymol. 235 (1994) 657-667.
9. [9]
  [9] K. Kuroda, G.A. Caputo, W.F. DeGrado, The role of hydrophobicity in the antimicrobial and hemolytic activities of polymethacrylate derivatives, Chem. Eur. J. 15 (2008) 1123-1133.
10. [10]
  [10] I. Sovadinova, E.F. Palermo, R. Huang, L.M. Thoma, K. Kuroda, Mechanism of polymer-induced hemolysis: nanosized pore formation and osmotic lysis, Biomacromolecules 12 (2011) 260-268.
11. [11]
  [11] W.F. DeGrado, G.F. Musso, M. Lieber, E.T. Kaiser, F.J. Ke′ zdy, Kinetics and mechanism of hemolysis induced by melittin and by a synthetic melittin analogue, Biophys. J. 37 (1982) 329-338.
12. [12]
  [12] A. Pokorny, P.F.F. Almeida, Kinetics of dye efflux and lipid flip-flop induced by d-lysin in phosphatidylcholine vesicles and the mechanism of graded release by amphipathic, a-helical peptides, Biochemistry 43 (2004) 8846-8857.
13. [13]
  [13] E.F. Palermo, D.K. Lee, A. Ramamoorthy, K. Kuroda, Role of cationic group structure in membrane binding and disruption by amphiphilic copolymers, J. Phys. Chem. B 115 (2011) 366-375.
14. [14]
  [14] M.T. Tosteson, S.J. Holmes, M. Razin, D.C. Tosteson, Melittin lysis of red cells, J. Membr. Biol. 87 (1985) 35-44.
15. [15]
  [15] M. Zasloff, Antimicrobial peptides of multicellular organisms, Nature 415 (2002) 389-395.
16. [16]
  [16] Y. Shai, Mode of action of membrane active antimicrobial peptides, Biopolymers 66 (2002) 236-248.
17. [17]
  [17] H.W. Huang, Action of antimicrobial peptides: two-state model, Biochemistry 39 (2000) 8347-8352.
18. [18]
  [18] G. Schwarz, H. Gerke, V. Rizzo, S. Stankowski, Incorporation kinetics in a membrane, studied with the pore-forming peptide alamethicin, Biophys. J. 52 (1987) 685-692.
19. [19]
  [19] K. Matsuzaki, O. Murase, K. Miyajima, Kinetics of pore formation by an antimicrobial peptide, magainin 2, in phospholipid bilayers, Biochemistry 34 (1995) 12553-12559.
20. [20]
  [20] T.H. Lee, C. Heng, M.J. Swann, et al., Real-time quantitative analysis of lipid disordering by aurein 1.2 during membrane adsorption, destabilisation and lysis, Biochim. Biophys. Acta 1798 (2010) 1977-1986.
21. [21]
  [21] S.J. Ludtke, K. He, H.W. Huang, Membrane thinning caused by magainin 2, Biochemistry 34 (1995) 16764-16769.
22. [22]
  [22] A.W. Bernheimer, Comparative kinetics of hemolysis induced by bacterial and other hemolysins, J. Gen. Physiol. 30 (1947) 337-353.
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