Dear Shen Wang ,

That is quite a challenging matter you try to address here.

If I understand your question properly you want to know what is the effect of membrane binding proteins beside the widespread and well documented effects of lipid transfer proteins.

When it comes to the effects of membrane proteins recently an interesting paper was published that discusses the current status about what we know about the effect of lipids on membrane protein function and to what degree the actual binding plays a role:

https://cen.acs.org/articles/95/i9/Lipids-affect-function-membrane-proteins.html

This paper includes parts of interviews with a number of key players in this field, you search for a number of their papers and you get some idea. I would say that it is feasible to assume that once membrane proteins bind (specifically) certain lipids this affects the lipid diffusion.

Related to peripheral membrane bound proteins your question is even harder to answer, since the enormous variety of functions of these type of proteins.

See for an excellent review:

Whited, A. M., & Johs, A. (2015). The interactions of peripheral membrane proteins with biological membranes. Chemistry and physics of lipids, 192, 51-59.

https://www.osti.gov/servlets/purl/1286884

Also the rising importance of the related family of amphitropic proteins might interest you:

https://www.tandfonline.com/doi/abs/10.1080/096876899294544

Article Identification and in silico analysis of helical lipid bindi...

Still in an attempt to answer your question: Relocalization of peripherally bound signaling and trafficking proteins respond to alterations at membrane surfaces. In other words these type of proteins bind to lipids during their function and by this way presumably affect lipid diffusion as well. See for example:

https://www.sciencedirect.com/science/article/pii/S0969212611004254

My impression is that your question has never been investigated directly but that there are some (educated) guesses that they (must) have an influence.

Hopefully this helps you a little bit further.

Dear Shen Wang ,

That is quite a challenging matter you try to address here.

If I understand your question properly you want to know what is the effect of membrane binding proteins beside the widespread and well documented effects of lipid transfer proteins.

When it comes to the effects of membrane proteins recently an interesting paper was published that discusses the current status about what we know about the effect of lipids on membrane protein function and to what degree the actual binding plays a role:

https://cen.acs.org/articles/95/i9/Lipids-affect-function-membrane-proteins.html

This paper includes parts of interviews with a number of key players in this field, you search for a number of their papers and you get some idea. I would say that it is feasible to assume that once membrane proteins bind (specifically) certain lipids this affects the lipid diffusion.

Related to peripheral membrane bound proteins your question is even harder to answer, since the enormous variety of functions of these type of proteins.

See for an excellent review:

Whited, A. M., & Johs, A. (2015). The interactions of peripheral membrane proteins with biological membranes. Chemistry and physics of lipids, 192, 51-59.

https://www.osti.gov/servlets/purl/1286884

Also the rising importance of the related family of amphitropic proteins might interest you:

https://www.tandfonline.com/doi/abs/10.1080/096876899294544

Article Identification and in silico analysis of helical lipid bindi...

Still in an attempt to answer your question: Relocalization of peripherally bound signaling and trafficking proteins respond to alterations at membrane surfaces. In other words these type of proteins bind to lipids during their function and by this way presumably affect lipid diffusion as well. See for example:

https://www.sciencedirect.com/science/article/pii/S0969212611004254

My impression is that your question has never been investigated directly but that there are some (educated) guesses that they (must) have an influence.

Hopefully this helps you a little bit further.

Hi Rob,

Thanks for your instructions. The reason for starting this discussion is that I have found different membrane-binding proteins have various effects on the diffusion of lipids. So I want to know whether there exists a universal mechanism or theory to predict the effect; or a certain effect is depended on specific molecules (proteins and lipids). I think I have got the answer from your replies. Thank you! @Rob Keller

I suppose the key issue is that both integral and peripheral membrane proteins bind many lipids with varying degrees of specificity and affinity. Lipids bound to proteins are expected to diffuse differently from free lipids. A peripheral membrane protein will thus also (in a multicomponent bilayer) likely have different lipid composition beneath it (e.g. enriched in PG, PS, CL, or PIPs) than the composition elsewhere. If large quantities of proteins are added on artificial bilayers, this amy also cause a shift in the composition of the remaining bilayer. And, of course, the bound lipid clusters will be obstacles to diffusion, so if much of the lipid is bound, there are many obstacles. Proteins binding to bilayers may also cause defects because of non-optimal packing into the lipid environment. Finally, if the lipid composition of the bilayer is already close to a phase boundary, the proteins that prefer certain types of lipids may by binding them form stable nuclei of one phase and the binding free energy may tip the system towards phase separation. This you might also see in lipid diffusion.