Freezing and piercing of in vitro asymmetric plasma membrane by α-synuclein
| Autor: | Paul Heo, Frederic Pincet |
|---|---|
| Přispěvatelé: | Mécanismes Moléculaires Membranaires, Laboratoire de physique de l'ENS - ENS Paris (LPENS (UMR_8023)), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Laboratoire de physique de l'ENS - ENS Paris (LPENS), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Sorbonne Université (SU)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Sorbonne Université (SU)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Synucleinopathies Membrane Fluidity Protein Conformation Parkinson's disease [SDV]Life Sciences [q-bio] animal diseases Medicine (miscellaneous) Plasma protein binding Electric Capacitance Protein Aggregation Pathological Article General Biochemistry Genetics and Molecular Biology Membrane Potentials Membrane Lipids Protein Aggregates Structure-Activity Relationship 03 medical and health sciences Membrane biophysics 0302 clinical medicine Lab-On-A-Chip Devices mental disorders Extracellular lcsh:QH301-705.5 Neurons Membrane potential Chemistry Cell Membrane technology industry and agriculture Membranes Artificial Microfluidic Analytical Techniques nervous system diseases Cytosol 030104 developmental biology Membrane nervous system lcsh:Biology (General) Membrane topology alpha-Synuclein Biophysics General Agricultural and Biological Sciences Hydrophobic and Hydrophilic Interactions 030217 neurology & neurosurgery Fluorescence Recovery After Photobleaching Protein Binding |
| Zdroj: | Communications Biology, Vol 3, Iss 1, Pp 1-8 (2020) Communications Biology Communications Biology, Nature Publishing Group, 2020, 3 (1), ⟨10.1038/s42003-020-0883-7⟩ |
| ISSN: | 2399-3642 |
| DOI: | 10.1038/s42003-020-0883-7 |
| Popis: | Synucleinopathies are neurological diseases that are characterized by the accumulation of aggregates of a cytosolic protein, α-synuclein, at the plasma membrane. Even though the pathological role of the protein is established, the mechanism by which it damages neurons remains unclear due to the difficulty to correctly mimic the plasma membrane in vitro. Using a microfluidic setup in which the composition of the plasma membrane, including the asymmetry of the two leaflets, is recapitulated, we demonstrate a triple action of α-synuclein on the membrane. First, it changes membrane topology by inducing pores of discrete sizes, likely nucleated from membrane-bound proteins and subsequently enlarged by proteins in solution. Second, protein binding to the cytosolic leaflet increases the membrane capacitance by thinning it and/or changing its relative permittivity. Third, α-synuclein insertion inside the membrane hydrophobic core immobilizes the lipids in both leaflets, including the opposing protein-free extracellular one. Heo and Pincet demonstrate the influence of α-synuclein aggregation on in vitro asymmetric membranes using a microfluidic setup. They show that synuclein aggregation on the asymmetric membranes leads to its thinning and formation of pores of discrete sizes and synuclein insertion immobilizes both the leaflets of the asymmetric membrane. |
| Databáze: | OpenAIRE |
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