We have been able to reconstitue actin dynamics in cell-sized confinement. We reveals the balancing mechanism for long-term network dynamics with a limited amount of building blocks (EMBO J. 2023). This work has been presented at several meeting (10) including a Keynote Lecture at the European Cytoskeleton meeting 2022. Alexandra Colin the first author of this publication obtained a PI permanent position at the CNRS in France in 2023. We were recently invited to write a review on this topic in Nature Cell Biology (review in press).
We have studied the role of actin filament crosslinking in the spatial integration of mechanical forces that ensures the adaptation of intracellular symmetry axes in accordance with the geometry of extracellular cues.( J. Cell Science, 2019).
In a recent study, we used a unique combination of micropatterning, local photoablation of contractile elements, global-force measurements, and theoretical modeling to describe finely the mechanics of the subcellular actin networks. We demonstrated that actin fibers were fully embedded along their entire length in a continuous and contractile network of cortical filaments. Therefore, the propagation of the contraction of these bundles throughout the entire cell was dependent on this embedding. In addition, these bundles appeared to originate from the alignment and coalescence of thin and unattached cortical actin filaments from the surrounding mesh. (Nature Materials 2021).
We have also studied how the actin architecture affects cargo positioning.We showed that the precision of cargo positioning is set by the gradient of net actin polarity in the network and by the run length of the cargo in an attached state. (Richard et al., PNAS, 2019).
We have also developed a method that allowed contactless and mask-free photo-micropatterning of electron microscopy grids for site-specific deposition of extracellular matrix-related proteins. Micropatterns generated predictable intracellular organization, allowing direct correlation between cell architecture and in-cell three-dimensional structural characterization of the underlying molecular machinery. (Toro-Nahuelpan et al., Nat. Methods, 2020).
Active cytoskeletal materials in vitro demonstrate self-organizing properties similar to those observed in their counterparts in cells. We have combined two networks (actin filaments and microtubules)in a dynamic system. In this composite, actin filaments can act as structural memory and, depending on the concentration of the components, microtubules either write this memory or get guided by it. The system is sensitive to external stimuli, suggesting possible autoregulatory behavior in changing mechanochemical environments. We thus establish an artificial active actin-microtubule composite as a system demonstrating architectural stability and plasticity (PNAS 2023).Ondre Kucera the first author of this publication obtained a lecturer position at the SETU in Ireland.
Finally, we have developed new tools (lipid patterning) to study the respective contribution of external and internal friction on the acto-myosin response. We are able to demonstrate how external friction can drive the symmetry of the contractile response (PNAS 2023).
