Sharp, localized phase transitions in single neuronal cells

Abstract

The origin of nonlinear responses in cells has been suggested to be crucial for various cell functions including the propagation of the nervous impulse. In physics, nonlinear behavior often originates from phase transitions. Evidence for such transitions on the single-cell level, however, has so far not been provided, leaving the field unattended by the biological community. Here, we demonstrate that single cells of a human neuronal cell line display all optical features of a sharp, highly nonlinear phase transition within their membrane. The transition is reversible and does not originate from protein denaturation. Triggered by temperature and modified by pH here, a thermodynamic approach strongly suggests that similar nonlinear state changes can be induced by other variables such as calcium or mechanical stress. At least in lipid membranes, such state changes are accompanied by significant changes in permeability, enzyme activity, elastic, and electrical properties.

The thermodynamic soliton theory of the nervous impulse and possible medical implications

“…As a consequence, in the transition the heat capacity, the compressibility (20), and the capacitance (32) reach maxima. Such transitions have been observed in lung surfactant (33,34), and in E.coli and b.subtilis membranes, nerve membranes from pigs, sheep, and rats (21) and in various cancer cell membranes (35) sharp transitions in human SH-SY5Ycells has been described (22). As we shall see, the existence of a melting transition slightly below body temperature is the prerequisite for the emergence of electromechanical solitons in nerve membranes.…”

“…Melting transitions in biological membranes can be shifted by changing pH. This has been found for both charged artificial members and biological membranes (21,22,38). Proton binding to charged lipids will lead to higher melting temperatures due to the reduction of the electrostatic surface potential.…”

“…Large changes in the extensive variables occur over a relatively small interval of the intensive variables. The transitions in biomembranes display a width of about 10 degrees (20,21), although there was a recent report claiming the membrane melting in a human cell line (SH-SY5Ycells) can occur over the much smaller temperature interval of 1 degree (22). Phase transitions and melting cannot be understood on the level of single molecules.…”

“…The transition temperature depends on lipid composition (20), on pressure (33), anesthetics concentration (24,36), the nature of membrane proteins (37), pH (21,22,38) and other environmental conditions. For instance, anesthetic drugs lower the transition temperature but hydrostatic pressure and lowering of pH increases transition temperatures (see section 4).…”

Enhancing functionalized liposome avidity to cells via lipid phase separation

“…Beyond mimicking the cell membrane, phase separation could also be used to engineer stimuli-responsive vesicles to enhance drug delivery. Phase separation can be induced through multiple stimuli including tension, 60 pH, 61 temperature, 62 small molecules, 63 peptides, 64 proteins, 65,66 and association with soluble oligomerizing molecules. 67, 68 Phase-separated vesicles could be used in conjunction with these stimuli to dynamically change the presentation of nanoparticle-bound ligands.…”