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Background

I am doing an undergraduate research project on the modelling and analysis of protein diffusion in plasma membranes. I am a physics and computer science student so naturally, I have many knowledge gaps in cell biology.

My understanding so far

I have been reading so many papers, but I still can't have a comprehensive general picture of protein diffusion in the membrane and what precisely that entails. From my understanding, the widely accepted model is the one with the underlying cytoskeleton actin mesh-like filaments which compartmentalize the plasma membrane. In this model then, are only transmembrane proteins affected in their diffusion by the mesh-like structure, which they sometimes touch (because the filaments are close to the inner side of the plasma membrane)? Moreover, peripheral proteins or other types of proteins, because they do not touch the actin filaments, do they just diffuse freely in a Brownian motion?

I understand that generally, proteins undergo diffusion either

  • freely (Brownian motion)
  • in a compartmentalized hop-diffusion way
  • or through irregular diffusion given lipid rafts (which generate concentration gradients).

Questions

But which proteins are we talking about, is it peripheral, transmembrane or else? Where are these proteins in the bilipid layer? And which direction are they diffusing, is it lateral diffusion or diffusion within the bilipid layer? Are all these 3 diffusion models going on at the same time but each affecting different categories of proteins? I can't have a clear picture of this ecosystem and would appreciate some insights on these questions so that I could begin my research with the simulations.

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You might want to go to the library and have a look at Alberts „Molecular Biology of the Cell“, an older edition of which is also available on the NCBI Bookshelf. Publication-grade knowledge might be too detailed at your point of education and might not fill in the „big picture“. We know a lot more about directed processes on the cell, so read about: endocytosis, glycocalyx, secretory pathway, receptor internalization/sequestration, clathrin coated pits, etc… I mean „Brownian motion“ is nice and all, but we‘re talking about living things here ;)

For your questions: Which proteins? Transmembrane proteins, receptors, pumps, pores, actin associated proteins, motor proteins (Myosin) etc.

Which direction? You’re looking at lateral diffusion (like lipid rafts). The bilipid layer is too thin to support anything else but lateral diffusion, since as far as I know, membrane proteins are pretty much „stuck“ at the membrane, unless they react to a signal pathway. If we‘re talking about selective pores/pumps, then movement through the membrane might be interesting to you. Also: flippase can flip lipid molecules from one lipid sheet up to the other.

Note that temperature has a big effect on cell membrane fluidity. Cells regulate the fluidity by embedding cholesterol into the lipid layer. One can measure the fluidity using FRAP (fluorescence recovery after photobleaching). That method might help you understand how diffusion in membranes works.

And yes, all the different diffusion models are going on at the same time. And so do tons of other processes. Welcome to molecular biology.

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