6533b855fe1ef96bd12b001d

RESEARCH PRODUCT

Protein denaturation caused by heat inactivation detrimentally affects biomolecular corona formation and cellular uptake

Artur GhazaryanSvenja MorsbachJulius MüllerJulius MüllerVolker MailänderVolker MailänderKatharina LandfesterJohanna SimonJohanna Simon

subject

0301 basic medicineProtein DenaturationHot TemperatureProtein Corona02 engineering and technologyMass SpectrometryMice03 medical and health sciencesProtein structureAdsorptionIn vivoAnimalsGeneral Materials ScienceChromatography High Pressure LiquidCalorimetry Differential ScanningChemistryBlood Proteins021001 nanoscience & nanotechnologyBlood proteinsProtein Structure TertiaryComplement systemClusterinRAW 264.7 Cells030104 developmental biologyBiophysicsNanoparticlesPolystyrenesElectrophoresis Polyacrylamide GelProtein CoronaNanocarriers0210 nano-technologyDrug carrier

description

Adsorption of blood proteins to the surface of nanocarriers is known to be the critical factor influencing cellular interactions and eventually determining the successful application of nanocarriers as drug carriers in vivo. There is an increasing number of reports summarizing large data sets of all identified corona proteins. However, to date our knowledge about the multiple mechanisms mediating interactions between proteins and nanocarriers is still limited. In this study, we investigate the influence of protein structure on the adsorption process and focus on the effect of heat inactivation of serum and plasma, which is a common cell culture procedure used to inactivate the complement system. As in general routine lab procedure, heat inactivation was performed at 56 °C for 30 min in order to denature heat labile proteins. When nanocarriers were exposed to native versus heat inactivated serum, we saw that the cellular uptake by macrophages was significantly affected. These results were then correlated with an altered corona composition that depended on the treatment of the protein source. In summary, we were able to prove that the protein structure is one of the key parameters determining protein corona formation.

10.1039/c8nr07424khttps://hdl.handle.net/21.11116/0000-0002-EFF2-021.11116/0000-0002-ABD9-9