The power and challenge of lipid (a)symmetry across the membrane and cell

Membrane asymmetry means that the two sides of membrane are structurally, physically and functionally different. Membrane asymmetry is largely related to the lipid sidedness and particularly to compositional (lipid head and acyl group) and physical (lipid packing order, charge, hydration and H-bonding interactions) differences in the inner and outer leaflets of lipid bilayer. Chemically, structurally and conformationally different non-covalent bound lipid molecules are physically fluid and deformable and enable to interact dynamically to form transient arrangements with asymmetry both perpendicular and parallel to the plane of the lipid bilayer. Although biological membranes are almost universally asymmetric however the asymmetry is not absolute since only drastic difference in the number of lipids per leaflet is found and symmetric arrangements are possible. Asymmetry is thought to direct and influence many core biological functions by altering the membrane's collective biochemical, biophysical and structural properties. Asymmetric transbilayer lipid distribution is found across all lipid classes, cells and near all endomembrane compartments. Why cell membranes are (a)symmetric and adopt almost exclusively highly entropically disfavored asymmetric state?