The description and understanding of the states of matter at the mesoscopic scale in biological systems is one of the major challenge of current biophysics for two main reasons. From the fundamental point of view, it is the scale of the transition between molecular chaos -molecules subjected to thermal agitation perform random processes- and the first organized structures -molecules form robust assemblies whose function are deterministic-. From the technical point of view, this scale has long remained inaccessible to observation; optical microscopy being intrinsically limited to a resolution of the order of 200 nanometers. After introducing the mesoscopic scale in cell biology, I will illustrate this challenge by presenting our results obtained on a signaling protein, the Rac1 protein. Cellular signaling pathways consists of cascades of biochemical reactions that allow the cell to regulate itself, feel its environment and act accordingly. Using single molecule techniques for super-resolution microscopy and optogenetic techniques, we have shown that the Rac1 protein forms nanoscopic aggregates of heterogeneous composition. The asymmetric distribution of these aggregates into subcellular gradients controls cellular processes such as migration. The concept that emerges from these results as well as those of the community is that molecular objects in biology are organized and interact collectively. The idea of stereospecific interaction, or more commonly "key-lock", must be extended to a new physics that integrates collective effects based on multivalent interactions of low affinities.
Amanda Remorino, Simon De Beco, Fanny Cayrac, ... Jean-Baptiste Masson, Maxime Dahan, Mathieu Coppey, Gradients of Rac1 Nanoclusters Support Spatial Patterns of Rac1 Signaling, Remorino et al., 2017, Cell Reports 21, 1922–1935, November 14, 2017 ª 2017 The Author(s).
S. de Beco, K. Vaidžiulytė, J. Manzi, F. Dalier, F. di Federico, G. Cornilleau, M. Dahan & M. Coppey, Optogenetic dissection of Rac1 and Cdc42 gradient shaping, NATURE COMMUNICATIONS | (2018) 9:4816 | DOI: 10.1038/s41467-018-07286-8 | www.nature.com/naturecommunications
spatial organization, temporal organization, mesoscopic scale, cellular signaling protein