IAM   02674
Unidad Ejecutora - UE
Biology Avoids Phase Separations
Journal of Physics A: Mathematical and Theoretical
IOP Publishing, Ltd
Año: 2011 p. 46468 - 46468
A textbook description of the cell reveals aqueous compartments with specific solutes (proteins, nucleic acids, saccharides and other organic molecules), separated by membranes scaffolded by lipids and crisscrossed by filaments of polymerized material. The traffic between compartments is controlled and selective, as is the nature, crowding and concentration of the solutes that may associate with one another. From a physical standpoint, one feature stands out in this biological context: there are no phase separations arising from precipitation of biological solutes, no matter how high their crowding or effective concentration. In fact, the only instance when phase separations are known to arise signal an aberrant process known as amyloidosis, leading to pathological conditions such as Alzheimer disease. In other words, phase separations do not occur spontaneously in biology and when they do, they signal a disease-related state. From a physicist´s perspective, it becomes imperative to understand what attributes of the biological interfacial tension enables solutes to interact and form functional complexes but also prevents them from aggregating. That is the scope of my contribution. The physical underpinnings of biological-water interfaces have remained elusive up to this point as thermodynamic concepts that are useful to describe homogeneous phase separation are inadequate to describe solutes that associate but do not precipitate. My nanoscale theoretical derivation introduces an elastic term that penalizes local changes in hydrogen-bonding coordination of interfacial water and allows for compensations due to favorable electrostatic interactions with the biological solute. The computation requires developing a surface integration procedure. Within this framework, the optimal configuration of water molecules at the biological interface minimizes a surface integral and hence a variational principle is established. Much work lies ahead as I try to incorporate this variational approach into the engineering of therapeutic molecules that can interfere with disease-related signaling traffic. This application entails effectively disrupting a signal-transduction protein complex by binding to one partner unit and reducing its interfacial tension with water so the target protein is no longer prone to form the complex. This work was originally published as a Fast Track Communication in J. Phys. A: Math. Theor. 44 292001.