The influence of maltose-modified poly(propylene imine) (PPI) dendrimers on dimyristoylphosphatidylcholine (DMPC) or dimyristoylphosphatidylcholine/dimyristoylphosphatidylglycerol (DMPC/DMPG) (3%) liposomes was studied. Fourth generation (G4) PPI dendrimers with primary amino surface groups were partially (open shell glycodendrimers - OS) or completely (dense shell glycodendrimers - DS) modified with maltose residues. As a model membrane, two types of 100nm diameter liposomes were used to observe differences in the interactions between neutral DMPC and negatively charged DMPC/DMPG bilayers. Interactions were studied using fluorescence spectroscopy to evaluate the membrane fluidity of both the hydrophobic and hydrophilic parts of the lipid bilayer and using differential scanning calorimetry to investigate thermodynamic parameter changes. Pulsed-filed gradient NMR experiments were carried out to evaluate common diffusion coefficient of DMPG and DS PPI in D2O when using below critical micelle concentration of DMPG. Both OS and DS PPI G4 dendrimers show interactions with liposomes. Neutral DS dendrimers exhibit stronger changes in membrane fluidity compared to OS dendrimers. The bilayer structure seems more rigid in the case of anionic DMPC/DMPG liposomes in comparison to pure and neutral DMPC liposomes. Generally, interactions of dendrimers with anionic DMPC/DMPG and neutral DMPC liposomes were at the same level. Higher concentrations of positively charged OS dendrimers induced the aggregation process with negatively charged liposomes. For all types of experiments, the presence of NaCl decreased the strength of the interactions between glycodendrimers and liposomes. Based on NMR diffusion experiments we suggest that apart from electrostatic interactions for OS PPI hydrogen bonds play a major role in maltose-modified PPI dendrimer interactions with anionic and neutral model membranes where a contact surface is needed for undergoing multiple H-bond interactions between maltose shell of glycodendrimers and surface membrane of liposome.

• Klíčová slova
• Glycodendrimer, Hydrogen bond, Ionic force, Liposomes, Model membranes,
• MeSH
• dendrimery chemie   metabolismus   MeSH
• difenylhexatrien chemie   MeSH
• diferenciální skenovací kalorimetrie MeSH
• dimyristoylfosfatidylcholin chemie   metabolismus   MeSH
• fluidita membrány MeSH
• fluorescenční polarizace MeSH
• fosfatidylglyceroly chemie   metabolismus   MeSH
• hydrofobní a hydrofilní interakce MeSH
• lipidové dvojvrstvy chemie   metabolismus   MeSH
• liposomy chemie   metabolismus   MeSH
• magnetická rezonanční spektroskopie MeSH
• maltosa chemie   metabolismus   MeSH
• membránové lipidy chemie   metabolismus   MeSH
• polypropyleny chemie   metabolismus   MeSH
• statická elektřina MeSH
• vodíková vazba MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• dendrimery MeSH
• difenylhexatrien MeSH
• dimyristoylfosfatidylcholin MeSH
• dimyristoylphosphatidylglycerol MeSH Prohlížeč
• fosfatidylglyceroly MeSH
• lipidové dvojvrstvy MeSH
• liposomy MeSH
• maltosa MeSH
• membránové lipidy MeSH
• poly(propyleneimine) MeSH Prohlížeč
• polypropyleny MeSH

In this study, vibrational circular dichroism (VCD) spectroscopy was employed for the first time to study the bilirubin (BR) interaction with model membranes and models for membrane proteins. An enantioselective interaction of BR with zwitterionic 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and sphingomyelin (SPM) liposomes was observed by VCD and electronic circular dichroism (ECD) complemented by absorption and fluorescence spectroscopy. The M-form of BR was preferentially recognized in the BR/DMPC system at concentration above 1×10(-4)M, for lower concentrations the P-form of BR was recognized by the DMPC liposomes. The VCD spectra also showed that the SPM liposomes, which represent the main component of nerve cell membrane, were significantly more disturbed by the presence of BR than the DMPC liposomes-a stable association with a strong VCD signal was observed providing the explanations for the supposed BR neurotoxicity. The effect of time and pH on the BR/DMPC or SPM liposome systems was shown to be essential while the effect of temperature in the range of 15-70°C was negligible demonstrating the surprisingly high temperature stability of BR when interacting with the studied membranes. The influence of a membrane protein was tested on a model consisting of poly-l-arginine (PLAG) bound in the α-helical form to the surface of 1,2-dimyristoyl-sn-glycero-3-phospho-(1'-rac-glycerol) liposomes and sodium dodecyl sulfate micelles. VCD and also ECD spectra showed that a variety of BR diastereoisomers interacted with PLAG in such systems. In a system of PLAG with micelles composed of sodium dodecyl sulfate, the M-form of bound BR was observed.

• Klíčová slova
• 1,2-dimyristoyl-sn-glycero-3-phospho-(1′-rac-glycerol), 1,2-dimyristoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycero-3-phospho-(1′-rac-glycerol), BR, Bilirubin–lipid interaction, Bilirubin–polypeptide interaction, DLS, DMPC, DMPG, DPPG, ECD, HSA, IR, LUV, Liposome, Membrane structure, PLAG, SDS, SPM, Sphingomyelin, UV–vis, VCD, Vibrational circular dichroism, bilirubin, dynamic light scattering, electronic circular dichroism, human serum albumin, infrared, large unilamellar vesicle, poly-l-arginine, sodium dodecyl sulfate, sphingomyelin, ultraviolet–visible, vibrational circular dichroism,
• MeSH
• bilirubin chemie   metabolismus   MeSH
• buněčná membrána metabolismus   MeSH
• cholesterol metabolismus   MeSH
• cirkulární dichroismus metody   MeSH
• fluorescenční spektrometrie MeSH
• fosfatidylcholiny metabolismus   MeSH
• lipidové dvojvrstvy chemie   metabolismus   MeSH
• liposomy MeSH
• micely MeSH
• molekulární modely MeSH
• spektroskopie infračervená s Fourierovou transformací MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bilirubin MeSH
• cholesterol MeSH
• fosfatidylcholiny MeSH
• lipidové dvojvrstvy MeSH
• liposomy MeSH
• micely MeSH

The influence of three generations of five different phosphonium carbosilane dendrimers and one ammonium carbosilane dendrimer as a reference (PMe3, PBu3, P(Et2)2(CH2)3OH, PPh3, P(MeOPh)3 and NMe3, peripheral functional groups) on dimyristoylphosphatidylcholine (DMPC) or a lipid mixture dimyristoylphosphatidylcholine/dimyristoylphosphatidylglycerol (DMPC/DMPG) of liposomes was studied by fluorescence polarization measurements and differential scanning calorimetry. All types of dendrimers interacted with neutral as well as negatively charged liposomes, but the strength and observed influence were different. Concentration, type of peripheral functional group modification and dendrimer generation were the main factors influencing the interaction. Generally, weak interactions as well as destabilization of the lipid membranes at low concentrations, regardless of liposome type, were observed in the case of DmPMe3, DmNMe3, DmPBu3 and DmP(Et2)2(CH2)3OH. Dendrimers with PPh3 and P(MeOPh)3 peripheral functional groups interacted much more strongly and increased the rigidity of liposomes. Electrostatic interactions, the hydrophobicity of substituents and charge shielding on the peripheral phosphonium group are important factors in the interaction. We suggest that, among the other types of dendrimers, the dendrimer with the P(MeOPh)3 peripheral functional group is a highly promising candidate for the design of a drug delivery system due to its positive charge, efficient interaction with lipidic membranes and low cytotoxicity.

• MeSH
• dendrimery chemie   MeSH
• glycerofosfolipidy chemie   MeSH
• hydrofobní a hydrofilní interakce MeSH
• lipidové dvojvrstvy chemie   MeSH
• liposomy chemie   MeSH
• molekulární struktura MeSH
• povrchové vlastnosti MeSH
• silany chemie   MeSH
• statická elektřina MeSH
• velikost částic MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• carbosilane MeSH Prohlížeč
• dendrimery MeSH
• glycerofosfolipidy MeSH
• lipidové dvojvrstvy MeSH
• liposomy MeSH
• silany MeSH