1. Jong Ah Kim, Christoffer Åberg, Anna Salvati, Kenneth A. Dawson
Role of cell cycle on the cellular uptake and dilution of nanoparticles in a cell population
Jong Ah Kim, Christoffer Åberg, Anna Salvati, Kenneth A. Dawson
This presentation contains a simple scheme of the cell cycle and shows nanoparticle uptake in a single cell, as it progresses through its cell cycle and undergoes cell division. The generation of the ranking (Fig. 1c) of the intracellular nanoparticle concentration for cells in the different cell cycle phases is also illustrated.
Supplementary Discussion

2. Cell Cycle
The cell cycle is a series of events that lead to cell division and replication, consisting of four phases: G1, S, G2 and M. The activation of each phase depends on the proper completion of the previous one. The cell cycle commences with the G1 phase, during which the cell increases its size. During the S phase the cell synthesizes DNA, and in the G2 phase it synthesizes proteins to prepare for cell division. Finally during the M phase the cell divides and the two daughter cells enter the G1 phase. Cells that have temporarily stopped dividing can enter a resting phase called G0.

3. cell growth, protein synthesis
Cell Cycle
G1 phase:
cell growth, protein synthesis
G0/G1

4. cell growth, protein synthesis
Cell Cycle
G1 phase:
cell growth, protein synthesis
G0/G1
S phase:
DNA synthesis S

5. Cell Cycle G2/M G0/G1 S G2 phase:
preparation for cell division, protein synthesis
G1 phase:
cell growth, protein synthesis
G2/M
G0/G1
S phase:
DNA synthesis S

6. Cell Cycle G2/M G0/G1 S G2 phase:
M phase:
mitosis (cell division)
G2 phase:
preparation for cell division, protein synthesis
G1 phase:
cell growth, protein synthesis
G2/M
G0/G1
S phase:
DNA synthesis S

7. Two new daughter cells in G1 phase
Cell Cycle
M phase:
mitosis (cell division)
G2 phase:
preparation for cell division, protein synthesis
Two new daughter cells in G1 phase
G2/M
G0/G1
S phase:
DNA synthesis S

8. Proliferation of a cell cultureS
G2/M
G0/G1
A cell culture is a mixture of cells in different phases of their cell cycle, simultaneously undergoing progression and cell division.
G0/G1 S
G2/M
Time

9. Proliferation of a cell cultureS
G2/M
G0/G1
A cell culture is a mixture of cells in different phases of their cell cycle, simultaneously undergoing progression and cell division.
G0/G1 S S
G2/M
G0/G1
G2/M
Cell division
Time

10. Proliferation of a cell cultureS
G2/M
G0/G1
A cell culture is a mixture of cells in different phases of their cell cycle, simultaneously undergoing progression and cell division.
G0/G1 S
G2/M S
G2/M
Cell division
G0/G1
G0/G1
G2/M
Cell division S
Time

11. Nanoparticle uptake in a cycling cell: example of a cell in G1 phase at the moment of exposure to nanoparticles S
G2/M
G0/G1

12. Nanoparticles enter the cells and accumulate in the lysosomes.
Nanoparticle uptake in a cycling cell: example of a cell in G1 phase at the moment of exposure to nanoparticles S
G2/M
G0/G1
Nanoparticles enter the cells and accumulate in the lysosomes.

13. Nanoparticle uptake in a cycling cell: example of a cell in G1 phase at the moment of exposure to nanoparticles S
G2/M
G0/G1
Nanoparticles enter the cells and accumulate in the lysosomes.
Nanoparticles are taken up throughout the cell cycle.

14. Nanoparticle uptake in a cycling cell: example of a cell in G1 phase at the moment of exposure to nanoparticles
Uptake rate in the different phases is similar. S
G2/M
G0/G1
Nanoparticles enter the cells and accumulate in the lysosomes.
Nanoparticles are taken up throughout the cell cycle.

15. Nanoparticle uptake in a cycling cell: example of a cell in G1 phase at the moment of exposure to nanoparticles
Upon cell division, cells dilute their intracellular nanoparticle concentration.
Uptake rate in the different phases is similar. S
G2/M
G0/G1
Nanoparticles enter the cells and accumulate in the lysosomes.
Nanoparticles are taken up throughout the cell cycle.

16. Nanoparticle uptake in a cycling cell: example of a cell in G1 phase at the moment of exposure to nanoparticles
Upon cell division, cells dilute their intracellular nanoparticle concentration.
Uptake rate in the different phases is similar. S
G2/M
G0/G1
Daughter cells will have (on average) half of the amount of nanoparticles compared to the parent cell.
Nanoparticles are taken up throughout the cell cycle.

17. Nanoparticle uptake in a cell population
G0/G1
G2/M S
Time

18. Nanoparticle uptake in a cell population
During the first 10 hours of uptake there is no major difference between the concentrations of nanoparticles in cells in the different phases.
G0/G1
G2/M S
Time

19. Nanoparticle uptake in a cell population
Once a significant fraction of the cells in G0/G1 are cells that divided during the exposure to nanoparticles, then the G0/G1 cells show a reduced nanoparticle concentration in comparison to the other phases.
G0/G1
G2/M S
G0/G1 S
G2/M
Cell division
Time

20. Nanoparticle uptake in a cell population
When cells that have divided begin to populate the S phase, then those cells also show a reduced intracellular nanoparticle concentration (compared to the cells in G2/M).
G0/G1 S
G2/M
G0/G1 S
G2/M
Cell division
Time