This manuscript comprises two sections:
1) The first section is my response (published online by the Journal of Neuroscience) to their paper.
2) The second is a my unpublished, speculative essay on the possible molecular mechanisms of brain phase transitions.
Tozzi, A. Dewetting transitions in mechanosensory channels (electronic response to de Nooij JC, Simon CM, Simon A, Doobar S, Steel KP, et al. The PDZ-Domain Protein Whirlin Facilitates Mechanosensory Signaling in Mammalian Proprioceptors. The Journal of Neuroscience, 18 February 2015, 35(7):3073-3084; doi:10.1523/JNEUROSCI.3699-14.2015).
Following the intriguing paper from de Nooij et al, I would like to highlight the hypothetical molecular mechanism of action of mechanosensory channels (Anishkin and Sukharev, 2004), namely, a state of dewetting transition: a concept borrowed from fluid mechanics (Sharmaa and Reiterb, 1996; Thompson, 2012). When water and ions are enclosed within the narrowest sub-nanometer confines of an ion channel's hydrophobic pore, they exhibit an odd behavior: in such a peculiar context, a stochastic liquid-vapor water phase transition occurs, near a critical point (Aryal et al. 2015). These transient vapor states are "dewetted", i.e., effectively devoid of water molecules within all or part of the pore. The decreased amount of water molecules in liquid state leads to impaired conductance, energetic barriers to ion transit, and closure of the channel, in a process termed "hydrophobic gating". The principles underlying the metastable dynamical state of hydrophobic gating require a very small radius of the tube and interactions with a strongly hydrophobic lining (Boreyko et al., 2011; Lapierre et al., 2013). Dewetting transitions, characterized by such an unusual behavior of water's supramolecular assembly, represent an increasingly important general principle that has been applied to countless morphological and/or functional biological structures, ranging from protein cavities (Young et al., 2010) to lipid droplets (Thiam et al., 2013) and the opening of macroapertures in endothelial cells (Gonzalez-Rodriguez et al., 2012), from extracellular matrix and glycocalix (Tanaka et al., 2005), to cell adhesion (Sackmann and Bruinsma, 2002) and lipid bilayers (Vargas et al., 2014).