Question

It's a pretty elementary concept, and when I first learned of itI don't think I had the foundations to even think of such aquestion, but I found myself the other day thinking about theamphipathic nature of the phospholipids in the plasma membrane andwhy it might be that lipid-soluble molecules don't stay in betweenthe layers (of the bilayer).

I know that simple diffusion is a response to a concentrationgradient, but consider a case where equilibrium is being restoredand lipid-soluble molecules are diffusing from whateverextracellular matrix through the membrane and into the cytosol.Towards the end of this process, when equilibrium is nearlyrestored and the last few molecules are making their way into thecell, the rate of diffusion for these last couple molecules will beslower than those that diffused when the concentration differencewas greater. Since the polar heads on the outside and inside of thebilayer are hydrophilic but the inner part, where the fatty acidtails are, is hydrophobic, what drives a molecule to leave thecozy, accepting, lipophilic environment of the middle (of thebilayer) to cross through the cytosolic-side rejecting polar headsand enter the cytosol?

I understand that initially these molecules were moving into thecell in response to a difference in intracellular vs extracellularconcentration, but I'm asking whether we would ever see a casewhere the gradient is nearly zero and a molecule in transit simplydecides to reside in between the layers instead of crossing all theway into the cell; as if moving through the cytosolic polar headside is not worth the effort to reduce a nearly-zero gradient tozero.

Please ask me if I can clarify my question in any way -- I'mfinding it difficult to phrase. I asked my professor (who has herdoctorate in toxicology & pharmacology) and she understood whatI was asking but didn't have an answer.