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Shaping tubes in cells

Identifieur interne : 000161 ( Hal/Checkpoint ); précédent : 000160; suivant : 000162

Shaping tubes in cells

Auteurs : Martin Lenz [France]

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RBID : Hal:tel-00541655

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Abstract

Membrane remodeling events are essential for the life of the cell, and involve membrane tubes shaped by proteins. We study three different configurations where such tubes appear. We first focus on the helical dynamin polymer, which encircles membrane tubes and severs them upon GTP hydrolysis. Dynamin recruitment is shown to depend on the membrane's curvature. We formulate hypotheses and propose experiments to understand the nucleation of the dynamin polymer and its interactions with the membrane. Dynamin's GTP-induced concerted conformational change is described using generalized hydrodynamics and seemingly contradictory experimental results are reconciled through mechanical arguments. The long-time dynamics of the dynamin-membrane tube is diffusive and dominated by an effective dynamin/membrane friction, which experiments confirm. Our second topic is the ESCRT-III complex, which tubulates flat membranes and assembles inside of them. We account for this deformation with a novel buckling instability arising when sticky curved filaments bind to the membrane. This hypothesis could be verified experimentally. A metastable regime for the flat membrane is uncovered, which the cell could use to quickly generate tubes. Thirdly, we turn to stereocilia, which are actin-based cellular protrusions essential for hearing. We predict their shape from the detachment dynamics of actin cross-linkers, which accounts for experimental data. If the cross-linkers are allowed to reattach, our model yields a dynamical phase transition towards unbounded growth and numerical simulations suggest an anomalous power-law divergence of the protrusion length.

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<abstract xml:lang="en">Membrane remodeling events are essential for the life of the cell, and involve membrane tubes shaped by proteins. We study three different configurations where such tubes appear. We first focus on the helical dynamin polymer, which encircles membrane tubes and severs them upon GTP hydrolysis. Dynamin recruitment is shown to depend on the membrane's curvature. We formulate hypotheses and propose experiments to understand the nucleation of the dynamin polymer and its interactions with the membrane. Dynamin's GTP-induced concerted conformational change is described using generalized hydrodynamics and seemingly contradictory experimental results are reconciled through mechanical arguments. The long-time dynamics of the dynamin-membrane tube is diffusive and dominated by an effective dynamin/membrane friction, which experiments confirm. Our second topic is the ESCRT-III complex, which tubulates flat membranes and assembles inside of them. We account for this deformation with a novel buckling instability arising when sticky curved filaments bind to the membrane. This hypothesis could be verified experimentally. A metastable regime for the flat membrane is uncovered, which the cell could use to quickly generate tubes. Thirdly, we turn to stereocilia, which are actin-based cellular protrusions essential for hearing. We predict their shape from the detachment dynamics of actin cross-linkers, which accounts for experimental data. If the cross-linkers are allowed to reattach, our model yields a dynamical phase transition towards unbounded growth and numerical simulations suggest an anomalous power-law divergence of the protrusion length.</abstract>
<abstract xml:lang="fr">La cellule remodèle sa membrane en permanence, ce qui entraîne la formation de tubes de membrane façonnés par des protéines. Nous étudions trois cas impliquant de tels tubes. Le premier est le polymère hélicoïdal de dynamine, qui enveloppe les tubes de membrane puis les coupe en hydrolysant le GTP. Nous montrons que le recrutement de la dynamine dépend de la courbure de la membrane. Nous formulons des hypothèses et proposons des expériences pour comprendre la nucléation du polymère de dynamine et ses interactions avec la membrane. Nous donnons une description hydrodynamique généralisée du changement de conformation coopératif de la dynamine induit par le GTP et réconcilions des résultats expérimentaux apparemment contradictoires par des arguments mécaniques. La dynamique aux temps longs de l'assemblage dynamine-membrane est diffusive et dominée par une friction effective entre dynamine et membrane, ce qui est confirmé expérimentalement. Notre second sujet est le complexe ESCRT-III, qui tubule les membranes planes de l'intérieur. Nous expliquons cette déformation par une instabilité de flambage inédite se produisant lorsque des filaments courbés qui s'attirent se lient à la membrane. Cette hypothèse peut être vérifiée expérimentalement. Un régime métastable pour la membrane plane est mis en évidence, et pourrait être utilisé par la cellule pour former des tubes rapidement. Troisièment, nous nous tournons vers les stéréocils, des protrusions cellulaires à base d'actine essentielles pour l'audition. Nous expliquons leur forme par la dynamique de détachement de protéines liant l'actine, et rendons compte de résultats expérimentaux. Si ces protéines sont autorisées à se réattacher, notre modèle prévoit une transition de phase dynamique vers un état de croissance non-bornée, et des simulations numériques suggèrent que la longueur des protrusions diverge en loi de puissance avec un exposant anormal.</abstract>
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