MechanoSpectrin · Dynamic and Mechanical Role of Spectrin in Membrane-Cytoskeleton Interplay
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2018-06-01 → 2020-05-31
- EU contribution
- €168,277
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Dynamic and Mechanical Role of Spectrin in Membrane-CytoskeletonInterplay
The spectrin-based membrane skeleton is a major component of the cell cortex. While expressed by all metazoans, its dynamic interactions with the other cortex components, including the plasma membrane or the acto-myosin cytoskeleton, are poorly understood. Here, I investigated how spectrin re-organizes spatially and dynamically under the membrane during changes in cell mechanics. We found spectrin and acto-myosin to be spatially distinct but cooperating during mechanical challenges, such as cell adhesion and contraction, or compression, stretch and osmolarity fluctuations, creating a cohesive cortex supporting the plasma membrane. Actin territories control protrusions and contractile structures while spectrin territories concentrate in retractile zones and low-actin density/inter-contractile regions, acting as a fence that organize membrane trafficking events. During MECHANOSPECTRIN, I unveiled the existence of a dynamic interplay between acto-myosin and spectrin necessary to support a mesoscale organization of the lipid bilayer into spatially-confined cortical territories during cell mechanoresponse. This line of research contributes to open new directions in the fields of morphodynamic regulation of cell shape and cell matrix interactions. Thus, it might lead to the identification of novel molecular target for cell signalling mechanisms linked to mechanoresponse during tissue/organ development or pathophysiological conditions with altered cell/tissue morphogenesis.
Data: CORDIS, © European Union
Project objective
Multicellular organisms have evolved complex mechanisms to sense and adapt to the surrounding environment by dynamically controlling cell shape and exert forces. While the most studied mechanisms are the Actin and Microtubule networks, there is poor understanding of a third system called Intermediate Filaments. In this context, a particularly overlooked mechano-sensing protein is spectrin, a resilient structural platform firstly described to maintain cell shape in erythrocytes and recently proposed to be involved in neuronal plasticity and maintenance of axon rigidity. Spectrin is ubiquitously expressed and the knock-out is detrimental. It is proposed to act as an elastic spring engaged in membrane-cytoskeleton connections, but molecular organisation and dynamic observations are unknown in most eukaryotic cell types. Particularly, is not understood how spectrin-based meshwork assemble-disassemble and react to mechanical perturbations, except from mostly static observations from erythrocytes and neurons. In this proposal, I plan to investigate spectrin dynamic during cell spreading, cell migration and its role in membrane mechanical adaptation. Using fibroblasts, a well characterized model system for membrane and cytoskeletal dynamic studies by Dr. Gauthier’s group, I aim to describe how spectrin dynamically contributes to cell shape changes, cell-substrate interaction and migration. With membrane-tension analysis by optical tweezers, time-resolved super-resolution microscopy, substrate micro-patterning techniques and various mechanical perturbations, I will unveil how spectrin reacts and contributes to mechanosensation and mechanotransduction. Overall, our results in fibroblast will elucidate the poorly understood contribution of Intermediate Filaments during mechanical adaptation and unveil why the spectrin family is evolutionary highly conserved and ubiquitously expressed.
Original text from CORDIS.
Participants
- IFOM-ISTITUTO FONDAZIONE DI ONCOLOGIA MOLECOLARE ETS · MilanoCoordinatorItaly
Links
Data: CORDIS, © European Union