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It is commonly told that, hydrophobic/ lipophilic/ nonpolar molecules can quite easily pass phospholipid bilayer, and hydrophilic (polar or ionic) molecules can't pass (when no protein aid that); because hydrophobic nature of the lipid.

But in the same logic, hydrophobic molecules shouldn't pass through the bilayer. Because there are 2 hydrophilic layers in the membrane. i.e.

layers of membrane

A and A' .

Then how the hydrophobic molecules can pass through A and A'?

I guess, it is due to thin diameter of A and A' . Is that?

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    $\begingroup$ Note that in a simple system like in that picture, you would find the highest concentration in the membrane, so in a way, the drugs does have difficulty getting through. $\endgroup$ – Eliane B. Oct 11 '16 at 19:05
  • $\begingroup$ @ElianeB. you mean hydrophobic molecules ('drugs' in your example) locked inside the lipid bilayer? $\endgroup$ – Always Confused Oct 11 '16 at 20:03
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    $\begingroup$ Yes. i.imgur.com/Peuv3Lk.png (Rang&Dale 7th ed, p.100). A and A' are not that different from the water around the bilayer. $\endgroup$ – Eliane B. Oct 11 '16 at 20:06
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Good question. This is my take.

It's not just the surface of the membrane that's polar. There is water (polar) on both sides of the membrane. In most animal cells there is also an unequal distribution of charges across the membrane. The environment outisde of the cell is typically positive due to an excess of positive ions, especially sodium. The inside of the cell is typically negative due to an excess of negative ions such as phosphate.

This means the hydrophobic molecules aren't any more at home in the environment outside, or inside, the membrane than they are at the surface. There's no reason to suppose any more repulsion at the surface. So, just due to their random kinetic motion they will find themselves at the membrane's surface, some with the necessary kinetic energy to cross.

There's another way to view this. We shouldn't think of the membrane as allowing hydrophobic substances to enter. We should think of it as NOT allowing hydrophyllic substance to enter without a proper ID check by proteins in the membrane.

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    $\begingroup$ It is also worth mentioning that some lipid molecules require a carrier that will deliver them to the target tissues. $\endgroup$ – WYSIWYG Oct 12 '16 at 6:51

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