Dataset Information

Nanocrystal facet modulation to enhance transferrin binding and cellular delivery.

ABSTRACT: Binding of biomolecules to crystal surfaces is critical for effective biological applications of crystalline nanomaterials. Here, we present the modulation of exposed crystal facets as a feasible approach to enhance specific nanocrystal-biomolecule associations for improving cellular targeting and nanomaterial uptake. We demonstrate that facet-engineering significantly enhances transferrin binding to cadmium chalcogenide nanocrystals and their subsequent delivery into cancer cells, mediated by transferrin receptors, in a complex biological matrix. Competitive adsorption experiments coupled with theoretical calculations reveal that the (100) facet of cadmoselite and (002) facet of greenockite preferentially bind with transferrin via inner-sphere thiol complexation. Molecular dynamics simulation infers that facet-dependent transferrin binding is also induced by the differential affinity of crystal facets to water molecules in the first solvation shell, which affects access to exposed facets. Overall, this research underlines the promise of facet engineering to improve the efficacy of crystalline nanomaterials in biological applications.

SUBMITTER: Qi Y

PROVIDER: S-EPMC7062909 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Nanocrystal facet modulation to enhance transferrin binding and cellular delivery.

Qi Yu Y Zhang Tong T Jing Chuanyong C Liu Sijin S Zhang Chengdong C Alvarez Pedro J J PJJ Chen Wei W

Nature communications 20200309 1

Binding of biomolecules to crystal surfaces is critical for effective biological applications of crystalline nanomaterials. Here, we present the modulation of exposed crystal facets as a feasible approach to enhance specific nanocrystal-biomolecule associations for improving cellular targeting and nanomaterial uptake. We demonstrate that facet-engineering significantly enhances transferrin binding to cadmium chalcogenide nanocrystals and their subsequent delivery into cancer cells, mediated by t ...[more]

PMID: 32152269

Similar Datasets

Project description:The bacterial bipartite transferrin receptor is an iron acquisition system that several important human and animal pathogens require for survival. It consists of the TonB-dependent transporter transferrin binding protein A (TbpA) and the surface lipoprotein transferrin binding protein B (TbpB). Curiously, the Tbps are only found in host-specific pathogens and are themselves host specific, meaning that they will bind to the transferrin of their host species but not to the transferrins of other animal species. While this phenomenon has long been established, neither the steps in the evolutionary process that led to this exquisite adaptation for the host nor the steps that could alter it are known. We sought to gain insight into these processes by studying Tbp specificity in Histophilus somni, an economically important pathogen of cattle. A past study showed that whole cells of H. somni specifically bind bovine transferrin but not transferrin from sheep and goats, two bovids whose transferrins share 93% amino acid sequence identity with bovine transferrin. To our surprise, we found that H. somni can use sheep and goat transferrins as iron sources for growth and that HsTbpB, but not HsTbpA, has detectable affinity for sheep and goat transferrins. Furthermore, a third transferrin binding protein found in H. somni, HsTbpA2, also showed affinity for sheep and goat transferrins. Our results suggest that H. somni TbpB and TbpA2 may contribute to broadening the host transferrin recognition range of H. somni IMPORTANCE Host-restricted pathogens infect a single host species or a narrow range of host species. Histophilus somni, a pathogen that incurs severe economic losses for the cattle industry, infects cattle, sheep, and goats but not other mammals. The transferrin binding proteins, TbpA and TbpB, are thought to be a key iron acquisition system in H. somni; however, despite their importance, H. somni TbpA and TbpB were previously shown to be cattle transferrin specific. In our study, we find that H. somni TbpB and another little-studied Tbp, TbpA2, bind sheep and goat transferrins, as well as bovine transferrin. Our results suggest that TbpB and TbpA2 may allow for host range expansion and provide a mechanism for how host specificity in Tbp-encoding pathogens can be altered.

Project description:IntroductionFrom viruses to organelles, fusion of biological membranes is used by diverse biological systems to deliver macromolecules across membrane barriers. Membrane fusion is also a potentially efficient mechanism for the delivery of macromolecular therapeutics to the cellular cytoplasm. However, a key shortcoming of existing fusogenic liposomal systems is that they are inefficient, requiring a high concentration of fusion-promoting lipids in order to cross cellular membrane barriers.ObjectivesToward addressing this limitation, our experiments explore the extent to which membrane fusion can be amplified by using the process of lipid membrane phase separation to concentrate fusion-promoting lipids within distinct regions of the membrane surface.MethodsWe used confocal fluorescence microscopy to investigate the integration of fusion-promoting lipids into a ternary lipid membrane system that separated into liquid-ordered and liquid-disordered membrane phases. Additionally, we quantified the impact of membrane phase separation on the efficiency with which liposomes transferred lipids and encapsulated macromolecules to cells, using a combination of confocal fluorescence imaging and flow cytometry.ResultsHere we report that concentrating fusion-promoting lipids within phase-separated lipid domains on the surfaces of liposomes significantly increases the efficiency of liposome fusion with model membranes and cells. In particular, membrane phase separation enhanced the delivery of lipids and model macromolecules to the cytoplasm of tumor cells by at least 4-fold in comparison to homogenous liposomes.ConclusionsOur findings demonstrate that phase separation can enhance membrane fusion by locally concentrating fusion-promoting lipids on the surface of liposomes. This work represents the first application of lipid membrane phase separation in the design of biomaterials-based delivery systems. Additionally, these results lay the ground work for developing fusogenic liposomes that are triggered by physical and molecular cues associated with target cells.

Dataset Information

Nanocrystal facet modulation to enhance transferrin binding and cellular delivery.

Publications

Nanocrystal facet modulation to enhance transferrin binding and cellular delivery.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure