I'm reading from Principles of Physical Biochemistry by Kensal E van Holde (1998-01-06) in order to review some biochemistry and work my way toward a more mathematical approach to understanding chemistry.

On page 18, chapter 1 (Biological Macromolecules), I read

"The structure of an integral membrane protein can be thought of as being inverted relative to the structure of a water soluble-protein, with the hydrophobic groups now exposed to the solvent, while the hydrophilic atoms form the core. An example of this inverted topology is an ionic channel (Figure 1.12). The polar groups that line the internal surface of the channel mimic the polar water solvent, thus alloweding charged ions to pass readily through an otherwise impenetrable bilayer."

I don't have a picture handy to show you Figure 1.12, but essentially it is a channel protein.

What's interesting to me about this passage is their use of the word topology. It reminded me of algrabraic topology's notion of a topology on a set, but I can't seem to state this membrane chemistry in terms of the mathematical formalism.

In algebraic topology, a topology $\tau$ on a set $X$ is a subset of the powerset $\mathcal{P}(X)$ where the elements of $\tau$ are open, meaning they satisfy

  1. Containing the original set and the empty set:$$X \in \tau, \emptyset \in \tau$$
  2. Unions of sets in the topology are closed. $$\{ U_i \}_{i \in I} \subseteq \tau \implies \bigcup_{i \in I} U_i \in \tau$$
  3. Closure under finite union. $$\{ U_i \}_{i=1}^n \subseteq \tau \implies \bigcap_{i=1}^n U_i \in \tau$$

My initial thinking on this is that the membrane could be one set, the extracellular matrix a second set, and the intracellular matrix as a third set. Each of these sets might be thought of as their own topologies, and that their mutual intersections should be empty so long as you cleanly partition the spaces. But then again, membranes have a lot of intermolecular spaces within them; seems structurally complicated.

While knowingly extrapolating beyond the original intended meaning of the authors, how can I model cellular membranes in terms of topology?

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    $\begingroup$ While an analysis in terms of formal topology is certainly possible, the word is here used more to mean "shape" and specifically where hydrophilic and hydrophobic residues are located relative to the surrounding medium. You have in essence two sets of residues (hydrophilic and hydrophobic) and one topological property (inside or outside). You might be overthinking this, depending on your objective. $\endgroup$ – Buck Thorn Apr 27 at 6:27
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    $\begingroup$ I would agree that you're over thinking this. As Buck indicated the only topological property is inside or outside, as for a circle. $\endgroup$ – MaxW Apr 27 at 7:28

As Buck Thorn and MaxW already said in the comments, there is less to it than the textbook excerpt might suggest. The use of the term topology in this context is non-mathematical, similar to when someone says there has been a quantum leap in product development.

The actual topology of most proteins is the same as that of a sphere, and the topology of the typical cartoon channel is that of a donut. Having hydrophilic residues in the channel or outside of the channel is not an inversion because those parts of the surface are topologically equivalent.

[OP] I can't seem to state this membrane chemistry in terms of the mathematical formalism.

That's because it is non-mathematical. There is some real topology associated with membranes, and that is the concept of inside and outside. Membrane proteins insert in one direction, and they don't "flip" directions over time, even though they are perfectly mobile to move around in the membrane (or have lipids move around them) while pointing in one direction or the other one. During endocytosis and exocytosis, the relative orientation of membrane proteins is conserved but inverted, so that parts that are inside organelles (such as glycosylation) end up on the outside of the plasma membrane.

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  • $\begingroup$ "actual topology of most proteins is the same as that of a sphere" - you are right of course, but sometimes "topology" is used instead of "fold" for proteins, again a little confusingly. In fact I've also seen the connectivity of small molecules called the "topology" for certain fields (like force field calculation) $\endgroup$ – gilleain Apr 27 at 10:32
  • $\begingroup$ Using topology for connectivity is great. Using it for the protein fold is not a rigorous use (unless you take the hydrogen bonds between strands in a beta sheet as fixed, or start discussing disulfide cross-links). However, the term has been widely used outside its mathematical definition, as you stated. A prominent example is the TOPS server: "The topology of a protein structure is a highly simplified description of its fold including only the sequence of secondary structure elements, and their relative spatial positions and approximate orientations." is far away from the original definition $\endgroup$ – Karsten Theis Apr 27 at 10:43
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    $\begingroup$ I agree about TOPS :) (I used to work on that project) I suspect that was originally driven by the 'T' in CATH : cathdb.info/wiki/doku/?id=glossary:topology $\endgroup$ – gilleain Apr 27 at 11:11

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