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Membrane-elasticity model of Coatless vesicle budding induced by ESCRT complexes.

Różycki B, Boura E, Hurley JH, Hummer G - PLoS Comput. Biol. (2012)

Bottom Line: On the basis of our model, we identify distinct mechanistic pathways for the ESCRT-mediated budding process.The bud size is determined by membrane material parameters, explaining the narrow yet different bud size distributions in vitro and in vivo.Our membrane elasticity model thus sheds light on the energetics and possible mechanisms of ESCRT-induced membrane budding.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.

ABSTRACT
The formation of vesicles is essential for many biological processes, in particular for the trafficking of membrane proteins within cells. The Endosomal Sorting Complex Required for Transport (ESCRT) directs membrane budding away from the cytosol. Unlike other vesicle formation pathways, the ESCRT-mediated budding occurs without a protein coat. Here, we propose a minimal model of ESCRT-induced vesicle budding. Our model is based on recent experimental observations from direct fluorescence microscopy imaging that show ESCRT proteins colocalized only in the neck region of membrane buds. The model, cast in the framework of membrane elasticity theory, reproduces the experimentally observed vesicle morphologies with physically meaningful parameters. In this parameter range, the minimum energy configurations of the membrane are coatless buds with ESCRTs localized in the bud neck, consistent with experiment. The minimum energy configurations agree with those seen in the fluorescence images, with respect to both bud shapes and ESCRT protein localization. On the basis of our model, we identify distinct mechanistic pathways for the ESCRT-mediated budding process. The bud size is determined by membrane material parameters, explaining the narrow yet different bud size distributions in vitro and in vivo. Our membrane elasticity model thus sheds light on the energetics and possible mechanisms of ESCRT-induced membrane budding.

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Membrane morphology diagram from the analytical solution obtained for the spherical cap approximation (lines) and from numerical energy minimizations (symbols).Results are shown for a Gaussian bending modulus fixed at . The green squares represent the flat membrane state. The magenta triangles correspond to ESCRT-coated membrane buds. The orange circles represent bare lipid buds with ESCRTs localized in the bud neck. The black solid lines are the coexistence lines, and the black dotted line represents the spinodal at which the energetic barrier to bud formation vanishes. Exemplary membrane shapes are shown for indicated points. The red and blue lines represent lipid domains and ESCRT-rich domains, respectively.
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pcbi-1002736-g002: Membrane morphology diagram from the analytical solution obtained for the spherical cap approximation (lines) and from numerical energy minimizations (symbols).Results are shown for a Gaussian bending modulus fixed at . The green squares represent the flat membrane state. The magenta triangles correspond to ESCRT-coated membrane buds. The orange circles represent bare lipid buds with ESCRTs localized in the bud neck. The black solid lines are the coexistence lines, and the black dotted line represents the spinodal at which the energetic barrier to bud formation vanishes. Exemplary membrane shapes are shown for indicated points. The red and blue lines represent lipid domains and ESCRT-rich domains, respectively.

Mentions: To make our model analytically tractable, we applied the spherical cap approximation, which is known to capture the energetics of unassisted membrane budding [45], [49]. In the spherical cap approximation, the energy functional Eq. (6) becomes a simple function whose minima can be found analytically (see Methods). The phase diagram that results from the energy minimization for displays three regimes which are shown in Fig. 2. For small line tensions (left side of Fig. 2), the membrane resists bending and remains flat. The lipid-segregated domain and the ESCRT-rich domain colocalize entirely. For large line tensions and large binding energies (top right corner of Fig. 2), the membrane buckles and forms an ESCRT-covered bud. Again and colocalize. For large and small (bottom right corner of Fig. 2), the minimum energy configurations are coatless buds with ESCRTs localized in the bud neck.


Membrane-elasticity model of Coatless vesicle budding induced by ESCRT complexes.

Różycki B, Boura E, Hurley JH, Hummer G - PLoS Comput. Biol. (2012)

Membrane morphology diagram from the analytical solution obtained for the spherical cap approximation (lines) and from numerical energy minimizations (symbols).Results are shown for a Gaussian bending modulus fixed at . The green squares represent the flat membrane state. The magenta triangles correspond to ESCRT-coated membrane buds. The orange circles represent bare lipid buds with ESCRTs localized in the bud neck. The black solid lines are the coexistence lines, and the black dotted line represents the spinodal at which the energetic barrier to bud formation vanishes. Exemplary membrane shapes are shown for indicated points. The red and blue lines represent lipid domains and ESCRT-rich domains, respectively.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475702&req=5

pcbi-1002736-g002: Membrane morphology diagram from the analytical solution obtained for the spherical cap approximation (lines) and from numerical energy minimizations (symbols).Results are shown for a Gaussian bending modulus fixed at . The green squares represent the flat membrane state. The magenta triangles correspond to ESCRT-coated membrane buds. The orange circles represent bare lipid buds with ESCRTs localized in the bud neck. The black solid lines are the coexistence lines, and the black dotted line represents the spinodal at which the energetic barrier to bud formation vanishes. Exemplary membrane shapes are shown for indicated points. The red and blue lines represent lipid domains and ESCRT-rich domains, respectively.
Mentions: To make our model analytically tractable, we applied the spherical cap approximation, which is known to capture the energetics of unassisted membrane budding [45], [49]. In the spherical cap approximation, the energy functional Eq. (6) becomes a simple function whose minima can be found analytically (see Methods). The phase diagram that results from the energy minimization for displays three regimes which are shown in Fig. 2. For small line tensions (left side of Fig. 2), the membrane resists bending and remains flat. The lipid-segregated domain and the ESCRT-rich domain colocalize entirely. For large line tensions and large binding energies (top right corner of Fig. 2), the membrane buckles and forms an ESCRT-covered bud. Again and colocalize. For large and small (bottom right corner of Fig. 2), the minimum energy configurations are coatless buds with ESCRTs localized in the bud neck.

Bottom Line: On the basis of our model, we identify distinct mechanistic pathways for the ESCRT-mediated budding process.The bud size is determined by membrane material parameters, explaining the narrow yet different bud size distributions in vitro and in vivo.Our membrane elasticity model thus sheds light on the energetics and possible mechanisms of ESCRT-induced membrane budding.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.

ABSTRACT
The formation of vesicles is essential for many biological processes, in particular for the trafficking of membrane proteins within cells. The Endosomal Sorting Complex Required for Transport (ESCRT) directs membrane budding away from the cytosol. Unlike other vesicle formation pathways, the ESCRT-mediated budding occurs without a protein coat. Here, we propose a minimal model of ESCRT-induced vesicle budding. Our model is based on recent experimental observations from direct fluorescence microscopy imaging that show ESCRT proteins colocalized only in the neck region of membrane buds. The model, cast in the framework of membrane elasticity theory, reproduces the experimentally observed vesicle morphologies with physically meaningful parameters. In this parameter range, the minimum energy configurations of the membrane are coatless buds with ESCRTs localized in the bud neck, consistent with experiment. The minimum energy configurations agree with those seen in the fluorescence images, with respect to both bud shapes and ESCRT protein localization. On the basis of our model, we identify distinct mechanistic pathways for the ESCRT-mediated budding process. The bud size is determined by membrane material parameters, explaining the narrow yet different bud size distributions in vitro and in vivo. Our membrane elasticity model thus sheds light on the energetics and possible mechanisms of ESCRT-induced membrane budding.

Show MeSH
Related in: MedlinePlus