19. Valuable insight into the distribution of the cells on the MCs,

cell confluency on single MCs and MC aggregate size can be

gleaned by fixing the MC bound cells with 10% neutral buff-

ered formalin solution (Sigma-Aldrich), staining the cells with

DAPI, and analyzing the MCs using the EVOS® FL Auto

Imaging System (Thermo Fisher Scientific). The staining pro-

cedure results in a shift in the excitation (λex) and emission

(λem) wavelength from 340 to 364 nm and 488 to 454 nm,

respectively, when DAPI selectively binds to double-stranded

DNA. This causes the cell nuclei to fluoresce. Thus, when

images taken using both the phase contrast and DAPI filter

lens at 4 magnification are merged, a single image showing

both the orientation of the MCs, as well as the location of

individual cell nuclei emerges. These images may then be

used to draw conclusions regarding cell distribution and MC

aggregation.

20. DAPI working solution is prepared by dissolving DAPI

(Roche) in WFI to a final concertation of 1.43 mmol L1.

This solution is light and temperature sensitive and should

therefore be stored in an opaque container at either 2 to 8 C

for up to 6 months or 15 to 25 C for up to 12 months.

21. Prepare a 0.3% Triton® X-100 working solution by diluting

30 μL of Triton® X-100 (Sigma-Aldrich) in 10 mL of sterile

DPBS. The working solution may be further improved

through sterile filtration (using a 0.22-μm syringe filter)

which removes any solid impurities introduced by the deter-

gent, as these may impact the quality of the images taken post-

staining.

22. Staining buffer is a mixture consisting of 19 mL autoMACS®

Rinsing Solution (Miltenyi Biotec) and 1 mL MACS BSA

Stock Solution (Miltenyi Biotec). The buffer contains sodium

azide as a preservative, serum to minimize nonspecific binding

of antibodies to the cells and ethylenediaminetetraacetic acid to

reduce cell aggregation.

Acknowledgments

The authors would like to thank Joel Rath and Riccardo Pianezza,

as well as Dr. Tiziano Tallone for their assistance and support with

the cell cultivation experiments. Finally, some figures were rendered

using the intuitive online application BioRender (see www.bio

render.com for more details).

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Misha Teale et al.