Biology subjects

Blanchoin, L.

Publications and source records attributed to Blanchoin, L..

4 recordsLinked to original sources

bioRxiv2018

Reconstitution of the equilibrium state of dynamic actin networks

Principles of regulation of actin network dimensions, fundamentally important for cell functions, remain unclear. We studied in vitro and in silico the effect of key parameters, actin density, ADF/Cofilin concentration and network width on the network length. In the presence of ADF/Cofilin, networks reached equilibrium and became globally treadmilling. At the trailing edge, the network disintegrated into large fragments. A mathematical model predicts the network length as a function of width, actin and ADF/Cofilin concentrations. Local depletion of ADF/Cofilin by binding to actin is significant, leading to wider networks growing longer. A single rate of breaking network nodes, proportional to ADF/Cofilin density and inversely proportional to the square of the actin density, can account for the disassembly dynamics. Selective disassembly of heterogeneous networks by ADF/Cofilin controls steering during motility. Our results establish general principles on how the dynamic equilibrium state of actin network emerges from biochemical and structural feedbacks.

cell biology↗

bioRxiv2018

Conditions for optimal mechanical power generation by a bundle of growing actin filaments

Bundles of actin filaments are central to a large variety of cellular structures, such as filopodia, stress fibers, cytokinetic rings or focal adhesions. The mechanical properties of these bundles are critical for proper force transmission and force bearing. Previous mathematical modeling efforts have focused on bundles rigidity and shape. However, it remains unknown how bundle length and thickness are controlled by external physical factors, and how the attachment of the bundle to a load affects its ability to transmit forces. In this paper, we present a biophysical model for dynamic bundles of actin filaments that takes into account individual filaments, their interaction with each other and with an external load. In combination with in vitro motility assays of beads coated with formins, our model allowed us to characterize conditions for bead movement and bundle buckling. From the deformation profiles, we determined key biophysical properties of tethered actin bundles, such as their rigidity and filament density. Our model also demonstrated that filaments undulate under lateral constraints applied by external forces or by neighboring filaments of the bundle. Last, our model allowed us to identify optimum conditions in filament density and barbed end tethering to the load for a maximal yield of mechanical power by a dynamic actin bundle.

biophysics↗

bioRxiv2018

Actin filaments regulate microtubule growth at the centrosome.

The centrosome is the main microtubule-organizing centre. It also organizes a local network of actin filaments. However, the precise function of the actin network at the centrosome is not well understood. Here we show that increasing densities of actin filaments at the centrosome of lymphocytes were correlated with reduced amounts of microtubules. Furthermore, lymphocyte activation resulted in centrosomal-actin disassembly and an increase in microtubule number. To further investigate the direct crosstalk between actin and microtubules at the centrosome, we performed in vitro reconstitution assays based on (i) purified centrosomes and (ii) on the co-micropatterning of microtubule seeds and actin filaments. The two assays demonstrated that actin filaments perturb microtubule growth by steric hindrance. Finally, we showed that cell adhesion and spreading leads to lower densities of centrosomal actin thus resulting in higher microtubule growth. Hence we propose a novel mechanism by which the number of centrosomal microtubules is regulated by cell adhesion and actin-network architecture.

cell biology↗

bioRxiv2018

Lattice defects induce microtubule self-renewal

The dynamic instability of microtubules is powered by the addition and removal of tubulin dimers at the ends of the microtubule. Apart from the end, the microtubule shaft is not considered to be dynamic. However recent evidence suggests that free dimers can be incorporated into the shaft of a microtubule damaged by mechanical stress. Here we explored whether dimer exchange was a core property of the microtubule lattice independently of any external constraint. We found that dimers can be removed from and incorporated into the lattice at sites along the microtubule shaft. Furthermore, we showed by experiment and by modeling that rapid dimer renewal requires structural defects in the lattice, which occur in fast growing microtubules. Hence long-lived microtubules have the capacity to self-renew despite their apparent stability and thereby can potentially regulate signaling pathways and structural rearrangements associated with tubulin-dimer exchange at sites along their entire length.

cell biology↗