Why are cannabis trichomes shaped like mushrooms? break cuticles

Terps are double-edged swords. They comprise a family of cannabinoid acids and terpenes, but are inversely toxic to cannabis plants. Luckily, terpene production takes place in trichomes — glandular hairs that cover your favorite frosty buds. And trichomes have many tricks to prevent toxic leakage of cannabinoids and terpenes, which includes their mushroom form.

Almost more important than the fungal form, however, are cellular transporters that transport CBGa and other nonpolar metabolites through cannabis trichomes. But four researchers have only recently elucidated part of this vital transport system. To better understand their discovery, this author spoke to one of the researchers, Sam Livingston, Ph.D. — a postdoc botanist and plant biologist from UBC.

Cyro-Scanning Electron Microscope (SEM) images of three types of trichomes including d.) stalked e.) sessile f.) bulbous. photo of dr Teagen D. Quilichini, courtesy of Sam Livingston | Willie (2)

Cannabinoid acids begin as non-polar metabolites within the cell matrix (within plastids) of a gland trichome. And their journey continues until they reach a cavity beneath the waxy cuticle—an entirely separate part of the trichome. However, the physical structure and internal mechanisms all serve a purpose.

That [cavity] This is where all non-polar metabolites are stored throughout plant development and when we harvest the buds for consumption.

Sam Livingston, Ph.D. Postdoc. botany ; plant biology. UBC. Samuel’s Laboratory, Keeling Lab.

Beyond the study, this author’s reasoning suggests that non-polar metabolites—particularly CBDa and limonene byproducts—act as natural pesticides. Cannabinoids also help plants survive by unintentionally attracting humans, who harvest and spread them around the world. In any case, the literature agrees that non-polar metabolites are inversely toxic to certain cells.

Non-polar metabolites are toxic to plant cells and they are toxic to other systems such as yeast, bacteria and even human cells. And the way they exert this toxicity could be through different mechanisms.

Sam

Cannabinoids also act as molecular antioxidants. (4) In contrast, their passage through the resinous trichomes of cannabis is likely associated with oxidative stress. (3, 5, 6) In addition, non-polar metabolites are oil-based in the synthetic pathway and can lead to toxic fluid disorders in plants.

We suggested that these metabolites likely get into membranes and somehow disrupt them – or alter their fluidity. And at high enough concentrations, we suspect that normal membrane components could fall apart.

Sam

How plants absorb herbicides

The reasons why non-polar botanical components induce autotoxicity in plant cells remain unclear. However, cellular transport within trichomes likely provides protection.

It’s strange that we have this interconnected supercellular oil factory that communicates clearly with itself, but is completely disconnected from everything below it.

Sam

Basal cells, which sit beneath the trichome’s secretory head, form a unique cell system atypical of the stalk or cuticle. And the different structures and mushroom shape of the trichomes help keep terpenes and cannabinoid acids away from defenseless plant cells with no storage cavity.

For this reason, we hypothesize that the supercells are separated from other plant cells – to prevent leakage and toxic effects from occurring in cells that cannot handle these metabolites.

Sam

Covering an umbrella of cannabinoids

Sam’s team grew THC-rich Purple Kush strains rather than CBD strains for their latest study. (1) Still, trichomes produce CBDa in the same part of the cell as THCa. (2, 3) Cells assemble both molecules once transporters bring CBGa to the surface. So Sam suggested that the process should apply to all cultivars, regardless of their cultivar or type.

THCa and CBDa both use CBGa as an input molecule. And the only thing that’s really different are the two enzymes that make either THCa or CBDa. [Enzymes] rearrange cannabinoids into various end products, and we suspect this is all happening inside the cell wall anyway.

Whether it’s THCa synthase in the cell wall of, say, Purple Kush, or CBDa synthase in the wall of a CBD strain like Finola. We hypothesize that the same mechanisms exist for CBGa transport inside the cell and transport CBGa outward to the cell wall.

Sam Livingston, postdoc.

For example, understanding how CBGa converts to THCa can help breeders find new tricks to create better CBG strains. And similar developments may focus on THCa production outside the polar membrane and its storage in the cavity under the cuticle. Nonetheless, stemmed scalp hair is essentially shaped like mushrooms to avoid the leakage of toxins. So keep your glands intact.

How trichomes from CBGa make CBDa and THCa

Cannabinoid and terpene production in a polar supercell found almost exclusively in trichomes is shown in the diagram. Photo courtesy of Sam Livingston, Cell Press, Current Biology Report. (1)

In the plastid of a cannabis trichome

• TPS-beta, an enzyme, converts an important terpene precursor known as GPP (geranyl pyrophosphate) within the plastids (yellow circle). The process spews out monoterpenes (MTs).
• In the presence of olivetolic acid (OA), the enzyme known as PT (aromatic prenyltransferase) consumes GPP and spews CBGa into the plastid membrane.

Between the plastid membrane and the cell wall

• Unusually large pores in the supercellular structures of the trichomes allow CBGa to penetrate to the cell surface.
• An unidentified ATP-binding cassette (ACB) family vehicle then propels CBGa to the surface — a critical journey.
• The ER (endoplasmic reticulum/green vesicles) and its junctions (cER/blue vesicles) must first allow the passage of CBGa to the surface.
• The ER passage is associated in most cases with a low exposure to oxidative stress. (3, 5, 6)

THCa outside the wall

Transitional Electron Microscope (TEM) scan looking into the terpene-producing plastid of a cannabis trichome. The lattice structure shows a paracrystalline core. Photo courtesy of Sam Livingston, Cell Press, Current Biology Report. (1)

• Lipid transfer proteins (LTPs) like to bring CBGa across the cell wall to THCAS (THC acid synthase enzymes).
• THCa production ends outside the cell under a detached pole cuticle.
• THCa and non-polar metabolites live in a storage cavity outside the cell wall, protected by the cuticle.
• Separate structures throughout the trichome, as well as transport vehicles within a polar supercell, prevent non-polar metabolites from reaching defenseless plant cells. (1, 3)

• Unrelated to cannabis and terpene, the Rab proteins, Ytp31 more than Ytp32, induce resistance to antifungal azole compounds in yeast cells (pseudohyphae). And Ytp31 traffic might depend on an ACBG transporter, PDR5P. (7, 8)

Separate terps from flowers

There are three different types of trichomes. Sitting atop the multicellular stem and base of the stalked trichome is an inner supercell. And this supercell is responsible for cannabinoid production. An outer waxy cuticle, while polar itself, is separate from the inner supercellular structure. The cuticle is another organ that surrounds the storage cavity and secretory interior of the trichome.

Trichomes produce modified terpenoids like THCa and CBDa. And of course, the glandular hairs of cannabis also make terpenes. And the mushroom shape that certain trichomes grow into helps keep non-polar metabolites away from the plant.

Let us know in the comments if you want to delve deeper into the transport system. And look at this story how the team froze trichomes using the most advanced techniques.

The cover photo is a multi-photon scan of stalked and sessile trichomes from a calyx of the Hindu Kush by Sam Livingston, Ph.D. and Postdoc, UBC | Wiley.

Sources

1. Samuel J Livingston, Kim H Rensing, Jonathan E Page, A Lacey Samuels. A polarized supercell produces specialized metabolites in cannabis trichomes. Current Biology, 2022;
2. Livingston SJ, Quilichini TD, Stand JK, et al. Cannabis glandular trichomes change morphology and metabolite content during flower maturation. Plant J. 2020;101(1):37-56. doi:10.1111/tpj.14516
3. Communication with Sam Livingston, Ph.D. and postdoc. 08/2022.
4. Borges RS, Batista J Jr, Viana RB, et al. Understanding the molecular aspects of tetrahydrocannabinol and cannabidiol as antioxidants. molecules. 2013;18(10):12663-12674. Published 14 Oct 2013. doi:10.3390/molecules181012663
5. Depaepe T, Hendrix S, Janse van Rensburg HC, Van den Ende W, Cuypers A, Van Der Straeten D. At the Crossroads of Survival and Death: The Reactive Oxygen Species-Ethylene-Sugar Triad and the Unfolded Protein Response. Trends Plant Sci. 2021;26(4):338-351. doi:10.1016/j.tplants.2020.12.007
6. A. Micci, Q. Zhang, X. Chang et al. Histochemical evidence for nitrogen-transfer endosymbiosis in non-photosynthetic cells of angiosperm leaves and inflorescences. Biology (Basel). 2022;11(6):876. Published June 7, 2022. doi:10.3390/biology11060876
7. Yoshiyuki Tsujimoto; Daisuke Takase; Hajime Okano; Naohiro Tomari; Kunihiko Watanabe; Hiroshi Matsui (2013). 1), –.doi:10.1016/j.jbiosc.2012.08.011
8. Paumi CM, Chuk M, Snider J, Stagljar I, Michaelis S. ABC transporters in Saccharomyces cerevisiae and their interactors: new technology advances the biology of the ABCC subfamily (MRP). Microbiol Mol Biol Rev. 2009;73(4):577-593. doi:10.1128/MMBR.00020-09