title: How do the full-generation poly(amido)amine (PAMAM) dendrimers activate blood platelets? Platelet membrane zeta potential and other membrane-associated phenomena.
abstract: We explored the hypothesis that zeta potential altered by polycations affects blood platelet activation and reactivity, the phenomena associated with membrane lipid fluidity and platelet mitochondrial bioenergetics. PAMAM dendrimers generation- and dose-dependently enhanced zeta potential of platelets (from -10.7 mV to -4.3 mV). Increased expressions of activation markers, P-selectin and the active complex αIIbβ3, as well as significantly enhanced fibrinogen binding occurred upon the in vitro incubation of blood platelets in the presence of PAMAMs G3 and G4 (resp. 62.1% and 69.4% vs. 1.4% and 2.7% in control for P-selectin, P<0.0001). PAMAM dendrimers increased fluidity of platelet membrane lipid bilayer, while they did not affect platelet mitochondria respiration. Increased platelet activation and their responses to agonists in vitro were statistically associated with the revealed alterations in zeta potential. Our results support the hypothesis that polycation-mediated "neutralized" zeta potential may underlie the activating effects of PAMAMs on blood platelets.
authors.affiliation: Department of Haemostasis and Haemostatic Disorders, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland. Electronic address: cezary.watala@umed.lodz.pl.
authors.forename: Cezary
authors.initials: C
authors.lastname: Watala
authors.affiliation: Department of Haemostasis and Haemostatic Disorders, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland.
authors.forename: Kamil
authors.initials: K
authors.lastname: Karolczak
authors.affiliation: Department of Haemostasis and Haemostatic Disorders, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland.
authors.forename: Hassan
authors.initials: H
authors.lastname: Kassassir
authors.affiliation: Department of Haemostasis and Haemostatic Disorders, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Siewiera
authors.affiliation: Department of Haemostasis and Haemostatic Disorders, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Maczynska
authors.affiliation: University of Lodz, Faculty of Biology and Environmental Protection, Department of Medical Biophysics, Pomorska 141/143, 90-236 Lodz, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Pieniazek
authors.affiliation: University of Lodz, Faculty of Biology and Environmental Protection, Department of Medical Biophysics, Pomorska 141/143, 90-236 Lodz, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Labieniec-Watala
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D002462:Cell Membrane; D050091:Dendrimers / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects*; D055815:Young Adult
chemical_list: D050091:Dendrimers; C104700:PAMAM Starburst; D010100:Oxygen
keywords: Blood flow; Electric charge; Membrane fluidity; Membrane potential; Mitochondrial respiration; Platelet activation