Programmed Self-Assembly of a Biochemical and Magnetic Scaffold to Trigger and Manipulate Microtubule Structures

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Programmed Self-Assembly of a Biochemical and Magnetic Scaffold to Trigger and Manipulate Microtubule Structures, Scientific REPOrtS | 7: 11344 | 2017

 

In living systems, proteins self-organize into macromolecular assemblies at various length scales to ensure the coordination of numerous biological functions in space and time. For instance, at the nanometer scale, protein scaffolds are central to trigger by proximity the activation of proteins involved in signal transduction. At the micrometric scales, multimeric interactions or repetitive interacting domains drive the organization of numerous functional structures, such as cytoskeleton fibres or organelles, with specific functional properties usually not found at the single molecule level. Numerous studies are now engaged to establish a clear link between biological multiscale assemblies and emergent functional properties. From this perspective the development of bio-based nanomaterials, produced from the programmed assembly of biomolecules as DNA, RNA, and proteins, offers novel tools to analyse and control the spatiotemporal properties of molecular and cellular processes, but also to engineer novel synthetic functionalities. For instance, DNA-based scaffolds, which provide very precise biomolecule spatial positioning, have been used to elucidate biophysical mechanisms underlying cytoskeleton motor activity or as fluorescent biosensors to probe the internal environment of living cells. Complementary, pioneer studies have demonstrated how synthetic protein scaffolds can modulate the cooperativity of ensembles of molecular motors, and artificially control metabolic flux or signalling pathways.

 

 

Our study, aiming to assemble an artificial and magnetic centrosome, raises interesting questions about the impact of multiscale assemblies on functional properties. For instance, we show that the mode of spatial organization of TPX2-ferritins, at the single nanocage level or assembled into micrometric scaffolds, influences the centring properties during microtubule self-organization, which eventually can impact the polarity of the overall cytoskeletal organization. This suggests that the fundamental property of the centring of microtubule asters may also depend on the local organization of the aster pole centre. Furthermore, our modular approach is generic and shows how artificial protein-based organelles can be engineered with emergent functional properties, suggesting its extension to mimic other protein-based organelles or to artificially trigger signalling pathways.

 

Finally, the transposition of our strategy into living cells will be powerful to target and manipulate specific proteins and cellular organelles by combining chemically induced dimerization and magnetic manipulation. A fully-genetically encoded strategy, avoiding in vitro biomineralisation and injection into cells, will require novel approaches to catalyse enhanced magnetic phases within cells. This will be necessary to overcome the limited magnetic properties of in vivo expressed ferritins that is a bottleneck for efficient magnetic manipulation. Beyond the development of new methods for spatiotemporal control, our strategy could also benefit other applications including biomedical imaging, biosensing, drug delivery, or the design of stimuli-responsive materials.

 

 

Résumé: 

Scientific REPOrtS | 7: 11344 | 2017

 

Artificial bio-based scaffolds offer broad applications in bioinspired chemistry, nanomedicine, and material science. One current challenge is to understand how the programmed self-assembly of biomolecules at the nanometre level can dictate the emergence of new functional properties at the mesoscopic scale. Here we report a general approach to design genetically encoded protein-based scaffolds with modular biochemical and magnetic functions. By combining chemically induced dimerization strategies and biomineralisation, we engineered ferritin nanocages to nucleate and manipulate microtubule structures upon magnetic actuation. Triggering the self-assembly of engineered ferritins into micrometric scaffolds mimics the function of centrosomes, the microtubule organizing centres of cells, and provides unique magnetic and self-organizing properties. We anticipate that our approach could be transposed to control various biological processes and extend to broader applications in biotechnology or material chemistry.

Equipe de rattachement 8640: 
Chimie Biophysique
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Programmed Self-Assembly of a Biochemical and Magnetic Scaffold to Trigger and Manipulate Microtubule Structures

 

Rémi Ducasse, Wei-An Wang, Marina Garcia-Jove Navarro, Nicolas Debons, Alexandra Colin, Jérémie Gautier, Jean-Michel Guigner, François Guyot & Zoher Gueroui

 

Scientific REPOrtS | 7: 11344 | 2017

 

DOI:10.1038/s41598-017-10297-y