Living Protein Ladder, showing different membrane receptor proteins
The rungs that ions and molecules travel in living cells
All cells have membranes that wrap the critical inside material into a sealed package. But cells cannot live behind a wall. Water, ions, sugars, and other molecules must continually cross it.
So living systems build passageways through the wall. These passageways are proteins. Those chains of amino acid molecules act as living protein ladders for the movement of the necessary building blocks into the cell as well as the movement of waste products out of the cell.
How do those protein ladders work?
Living amino acid rungs
Look inside one of these proteins and the passageway is not empty. Amino-acid side chains project into it. Their atoms create a sequence of places where a passing ion or molecule can interact.
Think of them as molecular handholds and footholds. A simplified image is that of a glucose molecule "walking" down the rungs of the protein ladder moving from outside the cell to the inside (the cytoplasm). The protein ladders also act as shuttling systems, with something like a dumb-waiter rapidly moving molecules from the outside to the cytoplasm.
Through multiple ways, the living protein ladders that live in our cell membranes allow our digested food to go from the intestine into the blood stream.
For example, small intestinal cells use those protein ladders (usually the sodium-glucose transporter proteins) to shuttle After a carbohydrate-rich meal, tens of quintillions of glucose molecules can cross the proximal small intestine every second. Spread among roughly a billion absorbing cells, that means an individual enterocyte participates in molecular traffic measured in billions of glucose molecules per second*.
When the rungs are broken
Our brains depend heavily on glucose. To reach the brain, glucose must first cross the blood–brain barrier using a specialized transporter called GLUT1.
Some babies are born with genetic changes that leave these glucose transporters unable to work normally — rather like having damaged rungs in the molecular ladder. Not enough glucose reaches the brain. The resulting condition, called GLUT1 deficiency syndrome, can cause seizures, developmental problems, and movement disorders
Matching the science to treat disease
Scientists have also learned how to deliberately block one of these molecular ladders. In the kidney, the SGLT2 transporter normally retrieves glucose from the filtered fluid and returns it to the blood.
Drugs such as empagliflozin (Jardiance) partially block that transporter. More glucose therefore remains in the urine and leaves the body, helping lower blood glucose.
Surprisingly, SGLT2 inhibitors also protect the kidneys and reduce heart-failure complications in many patients. Those benefits extend beyond simply lowering blood glucose. Exactly how all of those benefits arise is still being investigated.
Conclusion
Proteins build molecular pathways through cell membranes, and precisely positioned atoms guide ions and molecules along those pathways.
* Human duodenal anatomy and glucose-absorption measurements suggest that the proximal small intestine can handle glucose traffic on the order of 10¹⁹ molecules per second. Dividing that traffic among hundreds of millions to roughly a billion absorptive enterocytes gives an order-of-magnitude estimate of billions to tens of billions of glucose molecules per cell per second.
References:
- Wang D, Sands T, Tang M, et al. Glucose Transporter Type 1 Deficiency Syndrome. GeneReviews. Updated March 2025. Excellent for GLUT1 deficiency.
- Chen S, Coronel R, Hollmann MW, Weber NC, Zuurbier CJ. Direct cardiac effects of SGLT2 inhibitors. Cardiovasc Diabetol. 2022 Mar 18;21(1):45. doi: 10.1186/s12933-022-01480-1.
- Neumiller JJ, Lienhard FJ, Alicic RZ, Tuttle KR. Clinical Evidence and Proposed Mechanisms for Cardiovascular and Kidney Benefits from Sodium-Glucose Co-transporter-2 Inhibitors. touchREV Endocrinol. 2022 Nov;18(2):106-115. doi: 10.17925/EE.2022.18.2.106.
AI assistance note: I used ChatGPT as an editing partner while developing this post. The thinking and original draft (and any remaining errors) are my own.
Image Credit: Juan Gaertner. Different membrane proteins: (left to right) Potassium channel, delta-opioid receptor, LDL receptor, acetylcholine receptor, histamine receptor. The LDL receptor has a large extracellular segment and is typically localized to the basolateral membrane. Shutterstock, 1090429940.