Surface Thermodynamics Reveals Selective Structural Information Storage Capacity of c-Fos-phospholipid Interactions

The surface properties of c-Fos, a regulator of normal and pathologic cell growth and a modulator of phospholipid metabolism, suggest that it has the potential to transduce information through molecular reorganization, placing the nature of its interaction with phospholipids at the basis of its possible effects at the membrane level. Previous studies established that c-Fos induces condensation and depolarization of PIP₂ films and expansion and hyperpolarization of PC. We have now explored more in depth the thermodynamic aspects of these lipid−protein interactions, finding that the mixtures have associated hysteresis. The analysis of the excess thermodynamic functions provides evidence of entropic−enthalpic compensations that result in a favorable enthalpic contribution derived from the interaction of c-Fos with PIP₂, which exceeds the unfavorable configurational entropy. On the contrary, favorable entropy terms dominate the interaction of c-Fos with PC over the unfavorable enthalpy. The free energy of hysteresis is stored as excess free energy. A shift in molecular packing-dependent surface reorganization, compared to that of ideally mixed films, indicates a gain in information content at the lipid−protein interface in mixed films of c-Fos with PIP₂ but not with PC. It is postulated that the free energy stored in these mixtures could act as a bidirectional structural information transducer for dynamic compression−expansion processes occurring on the membrane surface.