matrixLife is a balancing act existing at the interface of opposing demands.  This realization comes from many directions and even finds itself entwined within the pillars of PICERAS.  As we saw earlier, PICERAS represents the seven universal pillars, or themes, found in all living cells.  One of these themes was Compartmentalization, where it is important to sequester the contents of the cell from its external environment, thereby allowing the cell to maintain an internal state that is completely different from the outside.  To compartmentalize the contents, we require a barrier that effectively cuts off all the internal activity of the cell from its outer environment.   But this poses a problem for other elements of PICERAS.  Adaptability, for example, is the process whereby cells communicate with the environment and respond to it in order to maintain their internal states.  If the cell was completely cut off from its environment, how could it detect and respond to it?  Furthermore, the pillar of Improvisation will work best if cells can communicate with their environment, evolving new solutions to the problems posed by this very environment the cell contents must be protected from.  So on one hand, the cell needs to be left alone, but on the other hand, the cell needs to be plugged in.  Shall it be an introvert or an extrovert?  Actually, the cell doesn’t have to choose because it has a very special “skin” – the membrane.

At first glance, a membrane might seem to be little more than a hodgepodge conglomeration, where two very different ingredients are tossed together to create a messy, oily film.  One ingredient consists of two layers of phospholipids.  These lipids form the very thin layer of oil and given that carbon-based nanotechnology exists in a water-based medium, the oily layer serves as an extremely effective barrier for molecules dissolved in the water.  Anything that is dissolved in water would rather stay embedded in the water than travel through a wall of oil. The lipid layers thus serve as the backbone of Compartmentalization, preventing all that dissolved material from leaving the cell and entering the cell.  It is thus no surprise why all cells require a lipid-based membrane without exception.  The other ingredient is the proteins.  The proteins can stick to one side of the phospholipids or penetrate them acting as conduits or channels connecting the inside of the cell with the environment.  Since the cells also controls the shape and activity of these proteins, it controls its connection with the environment.  The proteins thus satisfy the needs of Adaptability and Improvisation.  And this explains why all membranes are embedded with many different proteins.

The need to insert proteins into the membrane poses another design problem for the cell.  Since all proteins are synthesized on ribosomes that are located in the cytoplasm of the cell, how do you get the proteins into the membranes?  Do you just make them in the cytoplasm and let them float to the membrane where they will insert themselves?  This is a bigger problem than you might think.  Cytoplasmic proteins are dissolved in water and thus fold up into structures with hydrophobic cores and an outer surface that is hydrophilic.  But proteins embedded in the membrane tend to be “inside-out.”  Their outer surface is hydrophobic, allowing them to interact with the surrounding lipids, while their inner channel-like regions are hydrophilic so they can conduct dissolved material across the membrane.  This means the cytoplasm doesn’t provide the correct arena for the proper folding of membrane proteins.  In fact, in the cytoplasm, proteins with oily surfaces would stick to each other, forming large and growing clumps of oily goo that would gunk up the machinery of the cytoplasm.

A further design problem comes to mind.  Consider the bacterium E. coli.   A typical cell contains about 24,000 ribosomes.  Each ribosome strings together 40 amino acids per second. Let’s imagine that at any given point in time, only half the ribosomes are actively translating.  Furthermore, we’ll have them synthesize proteins with an average length of 200 amino acids. This would mean that about 2400 proteins were being added to the cytoplasm every second.  The newly made proteins part of this massive and constant stream have three possible fates: 1) remain in the cytoplasm; 2) be inserted into the membrane or; 3) be secreted out of the cell.  Roughly 20-30% of the proteins will end up in the membrane and about 500 proteins per second will be secreted.  The design problem is that of sorting all these proteins on a moment-by-moment basis to ensure they all reach their proper destination.

The obvious engineering solution to these twin problems is to design a device that would allow the ribosome to interface with the membrane on an “as needed” basis.  That it can insert membrane proteins or secrete proteins when appropriate, but remain in the cytoplasm when it is time to make cytoplasmic proteins.  It turns out that all cells have such a device, solving both the problem of relying on a cytoplasmic machine to make proteins that belong in the membrane and the problem of sorting thousands of proteins that are made every second – the signal recognition particle and its receptor.

2 responses to “Connections

  1. It is simply fascinating that molecular machines like SRP that sort proteins to the destined membrane are able to solve this twin design problem. And now we are at a level of quantification and mechanistic dissection that is helping to figure out the detailed molecular mechanisms. I look forward to your next installments.

  2. Yes, the fact that such a relatively simple device simultaneously solves two serious design problems echoes the rational essence of the system.

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