ON THE PRINCIPLES OF FUNCTIONAL ORDERING IN BIOLOGICAL-MEMBRANES

Integrating the available data on lipid-protein interactions and ordering in lipid mixtures allows to emanate a refined model for the dynamic organization of biomembranes. An important difference to the fluid mosaic model is that a high degree of spatio-temporal order should prevail also in liquid crystalline, ''fluid'' membranes and membrane domains. The interactions responsible for ordering the membrane lipids and proteins are hydrophobicity, coulombic forces, van der Waals dispersion, hydrogen bonding, hydration forces and steric elastic strain. Specific lipid-lipid and lipid-protein interactions result in a precisely controlled yet highly dynamic architecture of the membrane components, as well as in its selective modulation by the cell and its environment. Different modes of organization of the compositionally and functionally differentiated domains would correspond to different functional states of the membrane. Major regulators of membrane architecture are proposed to be membrane potential controlled by ion channels, intracellular Ca2+, pH, changes in lipid composition due to the action of phospholipases, cell-cell coupling, as well as coupling of the membrane with the cytoskeleton and the extracellular matrix. Membrane architecture is additionally modulated due to the membrane association of ions, lipo- and amphiphilic hormones, metabolites, drugs, lipid-binding peptide hormones and amphitropic proteins. Intermolecular associations in the membrane and in the membrane-cytoskeleton interface are further selectively controlled by specific phosphorylation and dephosphorylation cascades involving both proteins and lipids, and regulated by the extracellular matrix and the binding of growth factors and hormones to their specific receptor tyrosine kinases. A class of proteins coined architectins is proposed, as a notable example the pp60src kinase. The functional role of architectins would be in causing specific changes in the cytoskeleton-membrane interface, leading to specific configurational changes both in the membrane and cytoskeleton architecture and corresponding to (a) distinct metabolic/differentiation states of the cell, and (b) the formation and maintenance of proper three dimensional membrane structures such as neurites and pseudopods.