Do I know anybody who can eli5 this paper?

"Capsaicin can regulate VDSC function by altering bilayer elasticity. [...] may underlie the promiscuous regulation of membrane protein function by capsaicin and capsazepine-and by amphiphilic drugs generally."

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@eleanorkonik At small doses, capsaicin (which is also what makes food hot) activates pain receptors. Upping the dose a little bit, it also changes how a lot of other cell-wall proteins work. A lot of these are also changeable by capsazepine, which is a synthetic substance that can also block capsaicin and turn off one kind of pain receptor.

Science dorks have long been scratching their heads over how these two rivals can influence so many other types of proteins.

So this new study is examining if one way (perhaps the one and only way, perhaps one of many) that capsaicin can affect these cell-wall proteins was by changing how stiff or elastic the fat is that those cell-wall proteins are hosted on.

This fat cell-wall is built by two layers. Fat sheets are like a knitted sock where there are two different sides to the textile: one side attracts water and the other repels it. But cell walls have two layers, and the outside is the side that attracts water, while the water-repellent sides are directly facing each other.

Both capsaicin and capsazepine decrease a marker called a sodium channel. In and of itself, the eggheads weren't super fascinated by these sodium channels, but they looked at them because it was a sign that the fat cell wall might be becoming floppy and loose.

This new study found that, for capsaicin specifically, this relationship matched up with how soapy molecules ("ampiphiles" that like soap can groove with both fat and water) have a similar thing going on (specifically the relation between wall floppiness and sodium channel inactivation). Triton X-100 is the soap that matches up the closest.

Those soaps, Triton X-100 and friends, warp the fat walls (the two layers wanna curve in opposite directions) which is what makes it floppier.

This study concluded that capsaicin makes cell walls floppier, which might explain the long-pondered mystery on how these two molecules (capsaicin and it's dark mirror) can mess with so many other proteins at once, which has been so weird. But since it floppifies the wall that those many other proteins are on, that explains why they are affected. 🎉

@Sandra thank you so much for this incredibly clear explanation!!

@eleanorkonik So by "promiscuous regulation" they mean that capsaicin, capsazepine, and other ampiphiles affect a lot of proteins. And ther proposed mechanism of this that the ampiphilic qualities—that is, being able to mess with both fat and water at the same time, soaps are ampiphiles since they help dissolve fat—makes the bilayer (the fat sheet that has hydrophobic layers facing each other and hydrophilic layers facing outwards) less elastic. The marker they're using to check for this decreased elasticity is a sodium channel, a voltage-dependent one to be specific (a "VDSC").
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