The lymphatic system is a network of branching vessels that regulate fluid balance and support the immune system. Its smallest capillaries, comprised of a single endothelial cell layer, must stay flexible to let fluid and immune cells pass while resisting rupture under pressure. These cells have a distinctive lobate shape, but researchers were unsure if this shape helps manage interstitial fluid pressure.
“It has been known for a long time that capillary lymphatic endothelial cells have a lobate shape, rather like oak leaves or jigsaw puzzle pieces. However, the reason for this unique morphology was not known,” biologist Taija Mäkinen at Uppsala University remarked in a press release.
The lymphatic endothelial cells overlap with one another, which enables the cells to withstand changes in fluid volumes.
Hans Schoofs
Intrigued by the shape similarities between mammalian lymphatic endothelial cells (LECs) and plant cells, Mäkinen and her colleagues sought insights from plant epidermal cells, which also endure pressure-induced strain from fluid fluxes to stay upright.
In a new study published in Nature, the researchers discovered that LECs not only share their lobate shape but also exhibit similar cytoskeletal structure and signaling pathway regulation—factors that help maintain capillary integrity.1 These findings show that this unique cellular shape is tied to an essential biological function.
Because lymphatic vessels ferry fluid and solutes, the researchers wanted to assess how LECs respond to stress during changes in fluid pressure. They repeatedly stretched cultured cells in multiple directions. The cells began to acquire a lobate shape and overlapped neighboring cells. Lobate cells exhibited less stress under pressure compared to non-lobate cells, indicating that this shape enhanced the cells’ resistance to mechanical strain.
To explore the cell-cell junctions that maintain the integrity of the vessel walls, the researchers examined the ear skin from mice. Using immunofluorescence, they noted that cadherin junctions, which help cells stick together, clustered in these overlapping regions like interlocking puzzle pieces. This arrangement likely allows vessels to expand and contract as fluid levels fluctuate.
To dig deeper into the structure of LECs, the researchers examined their cytoskeleton. Single-cell RNA sequencing revealed that capillary LECs had higher expression of genes linked to actin, spectrin, and microtubules—key components of the cytoskeleton—compared to other LEC subtypes.
The team also noticed a striking pattern in the cytoskeletal filament distribution. Concave regions within the cell were packed with microtubules for stability, while convex lobes were rich in actin, supporting dynamic growth and expansion. This mirrored the cellular architecture seen in plant epidermal cells, where Rho guanosine triphosphatases (Rho GTPases) regulate these structures.2,3
To explore whether Rho GTPase signaling played a similar role in mammalian LECs, the researchers focused on a Rho GTPase, cell division cycle 42 (Cdc42), which is a crucial regulator of actin and microtubules. In mice that lacked the Cdc42 gene, LECs lost their characteristic shape and vessel integrity suffered, as evidenced by reduced cellular overlap.
“This indicates that the lymphatic capillaries need this overlap for the vessel to be able to expand without rupturing when the fluid pressure rises,” explained Mäkinen. The study’s findings underscore how this unique lobate shape is due to its specialized function for structural stability.
- Schoofs H, et al. Dynamic cytoskeletal regulation of cell shape supports resilience of lymphatic endothelium. Nature. 2025.
- Liu S, et al. Solving the puzzle of shape regulation in plant epidermal pavement cells. Annu Rev Plant Biol. 2021;72:525-550.
- Majda M, et al. Mechanochemical polarization of contiguous cell walls shapes plant pavement cells. Dev Cell. 2017;43(3):290-304.e4.
