Role of endocytosis in sonoporation-mediated membrane permeabilization and uptake of small molecules: a electron microscopy study
| Autor: | Aya Zeghimi, Ayache Bouakaz, Jean-Michel Escoffre |
|---|---|
| Přispěvatelé: | Escoffre, Jean-Michel, Appel à projets générique - Délivrance ciblée par ultrasons - - SOUNDELIVERY2014 - ANR-14-CE17-0008 - Appel à projets générique - VALID, Image-controlled Ultrasound-induced Drug Delivery - SONODRUGS - - EC:FP7:NMP2008-11-01 - 2012-10-31 - 213706 - VALID, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours (UT), This work was supported by grants from Inserm, the ANR Soundelivery (ANR-14-CE17-0008-01) and the European Commission FP7 Program SONODRUGS (NMP4-LA-2008-213706)., ANR-14-CE17-0008,SOUNDELIVERY,Délivrance ciblée par ultrasons(2014), European Project: 213706,EC:FP7:NMP,FP7-NMP-2007-LARGE-1,SONODRUGS(2008), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Rok vydání: | 2015 |
| Předmět: |
[SDV.BIO]Life Sciences [q-bio]/Biotechnology
Cell Membrane Permeability Cell Biophysics 02 engineering and technology [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology Endocytosis 03 medical and health sciences Microscopy Electron Transmission Structural Biology In vivo medicine sonoporation Molecular Biology [SDV.BC] Life Sciences [q-bio]/Cellular Biology 030304 developmental biology 0303 health sciences Microbubbles electron microscopy Cell Biology [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences 021001 nanoscience & nanotechnology Small molecule In vitro Cell biology [SDV.BIO] Life Sciences [q-bio]/Biotechnology [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences small molecules medicine.anatomical_structure Membrane Ultrasonic Waves Microscopy Electron Scanning membrane permeabilization 0210 nano-technology Sonoporation Intracellular |
| Zdroj: | Physical Biology Physical Biology, Institute of Physics: Hybrid Open Access, 2015, 12 (6), pp.066007. ⟨10.1088/1478-3975/12/6/066007⟩ Physical Biology, 2015, 12 (6), pp.066007. ⟨10.1088/1478-3975/12/6/066007⟩ |
| ISSN: | 1478-3975 1478-3967 |
| DOI: | 10.1088/1478-3975/12/6/066007⟩ |
| Popis: | A Zeghimi and JM Escoffre have contributed equally to this work.; International audience; Sonoporation is a physical method that has been successfully used to deliver drugs into living cells both in vitro and in vivo for experimental and therapeutic purposes. Despite numerous studies on this topic, often reporting successful outcomes, very little is known about the mechanisms involved in the hypothesized membrane permeabilization processes. In this study, electron microscopy was used to investigate the ultra-structural modifications of cell membranes, induced by sonoporation. Here, we demonstrate that sonoporation in the presence of microbubbles induces the formation of a significant number of transient and permeant structures at the membrane level. These structures were transient with a half-life of 10 min and had a heterogeneous size distribution ranging from a few nanometers to 150 nm. We demonstrated that the number and the size of these structures were positively correlated with the enhanced intracellular uptake of small molecules. In addition, we showed that these structures were associated with caveolae-dependent endocytosis for two thirds of the recorded events, with the remaining one third related to non-specific routes such as membrane disruptions as well as caveolae-independent endocytosis. In conclusion, our observations provide direct evidences of the involvement of caveolae-endocytosis in cell membrane permeabilization to small molecules after sonoporation. |
| Databáze: | OpenAIRE |
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