of Rho GTPase activities during cell protrusion. Nature 461:99–103. https://doi.org/
10.1038/nature08242
7. Te Kuo C, Liu HK, Huang GS, Chang CH,
Chen CL, Chen KC, Huang RYJ, Lin CH,
Lee H, Huang CS, Wo AM (2014) A spatiotemporally defined in vitro microenvironment
for controllable signal delivery and drug
screening. Analyst 139:4846–4854. https://
doi.org/10.1039/c4an00936c
8. Wu YI, Frey D, Lungu OI, Jaehrig A,
Schlichting I, Kuhlman B, Hahn KM (2009)
A genetically encoded photoactivatable Rac
controls the motility of living cells. Nature
461:104–108.
https://doi.org/10.1038/
nature08241
9. Kennedy MJ, Hughes RM, Peteya LA,
Schwartz JW, Ehlers MD, Tucker CL (2010)
Rapid blue-light-mediated induction of protein interactions in living cells. Nat Methods
7:973–975. https://doi.org/10.1038/nmeth.
1524
10. Levskaya A, Weiner OD, Lim WA, Voigt CA
(2010) Spatiotemporal control of cell signalling using a light-switchable protein interaction. Nature 461:1–5. https://doi.org/10.
1038/nature08446
11. Guntas G, Hallett RA, Zimmerman SP,
Williams T, Yumerefendi H, Bear JE, Kuhlman
B (2015) Engineering an improved lightinduced dimer (iLID) for controlling the localization and activity of signaling proteins. Proc
Natl Acad Sci 112:112–117. https://doi.org/
10.1073/pnas.1417910112
12. Toettcher JE, Voigt CA, Weiner OD, Lim WA
(2011) The promise of optogenetics in cell
biology: interrogating molecular circuits in
space and time. Nat Methods 8:35–38.
https://doi.org/10.1038/nmeth.f.326
13. Valon L, Etoc F, Remorino A, Di Pietro F,
Morin X, Dahan M, Coppey M, di Pietro F,
Morin X, Dahan M, Coppey M (2015) Predictive spatiotemporal manipulation of signaling
perturbations using optogenetics. Biophys J
109:1785–1797. https://doi.org/10.1016/j.
bpj.2015.08.042
14. de Beco S, Vaidz ˇiulyte ˙ K, Manzi J, Dalier F, di
Federico F, Cornilleau G, Dahan M,
Coppey M, De Beco S, Manzi J, Dalier F,
Cornilleau G, Dahan M, Coppey M (2018)
Optogenetic dissection of Rac1 and Cdc42
gradient shaping. Nat Commun 9:1–13.
https://doi.org/10.1038/s41467-01807286-8
15. Valon L, Marı ´n-Llaurado ´ A, Wyatt T,
Charras G, Trepat X, Marin-Llaurado A,
Wyatt T, Charras G, Trepat X (2017) Optogenetic control of cellular forces and mechanotransduction. Nat Commun 8:14396. https://
doi.org/10.1038/ncomms14396
16. Lee S, Park H, Kyung T, Kim NY, Kim S,
Kim J, Do Heo W (2014) Reversible protein
inactivation by optogenetic trapping in cells.
Nat Methods 11:633–636. https://doi.org/
10.1038/nmeth.2940
17. Taslimi A, Vrana JD, Chen D, Borinskaya S,
Mayer BJ, Kennedy MJ, Tucker CL (2014) An
optimized optogenetic clustering tool for
probing protein interaction and function. Nat
Commun 5:4925. https://doi.org/10.1038/
ncomms5925
18. Grusch M, Schelch K, Riedler R, Reichhart E,
Differ C, Berger W, Ingle ´s-Prieto A ´ , Janovjak
H (2014) Spatio-temporally precise activation
of engineered receptor tyrosine kinases by
light. EMBO J 33:1713–1726. https://doi.
org/10.15252/embj.201387695
19. Bugaj LJ, Spelke DP, Mesuda CK, Varedi M,
Kane RS, Schaffer DV (2015) Regulation of
endogenous transmembrane receptors through
optogenetic Cry2 clustering. Nat Commun
6:6898.
https://doi.org/10.1038/
ncomms7898
20. Zhou XX, Fan LZ, Li P, Lin MZ (2017) Optical control of cell signaling by single-chain
photoswitchable kinases. Science 355:836–842
21. Leopold AV, Chernov KG, Verkhusha VV
(2018) Optogenetically controlled protein
kinases for regulation of cellular signaling.
Chem Soc Rev 47:2454–2484. https://doi.
org/10.1039/c7cs00404d
22. Strickland D, Lin Y, Wagner E, Hope CM,
Zayner J, Antoniou C, Sosnick TR, Weiss EL,
Glotzer M (2012) TULIPs: tunable, lightcontrolled interacting protein tags for cell biology. Nat Methods 9:379–384. https://doi.
org/10.1038/nmeth.1904
23. Hallett RA, Zimmerman SP, Yumerefendi H,
Bear JE, Kuhlman B (2016) Correlating
in vitro and in vivo activities of light-inducible
dimers: a cellular Optogenetics guide. ACS
Synth Biol 5:53–64. https://doi.org/10.
1021/acssynbio.5b00119
24. Filonov GS, Piatkevich KD, Ting L-M,
Zhang J, Kim K, Verkhusha VV (2011) Bright
and stable near-infrared fluorescent protein for
in vivo imaging. Nat Biotechnol 29:757–761.
https://doi.org/10.1038/nbt.1918
Control of Cell Migration Using Optogenetics
425
10.1038/nature08242
7. Te Kuo C, Liu HK, Huang GS, Chang CH,
Chen CL, Chen KC, Huang RYJ, Lin CH,
Lee H, Huang CS, Wo AM (2014) A spatiotemporally defined in vitro microenvironment
for controllable signal delivery and drug
screening. Analyst 139:4846–4854. https://
doi.org/10.1039/c4an00936c
8. Wu YI, Frey D, Lungu OI, Jaehrig A,
Schlichting I, Kuhlman B, Hahn KM (2009)
A genetically encoded photoactivatable Rac
controls the motility of living cells. Nature
461:104–108.
https://doi.org/10.1038/
nature08241
9. Kennedy MJ, Hughes RM, Peteya LA,
Schwartz JW, Ehlers MD, Tucker CL (2010)
Rapid blue-light-mediated induction of protein interactions in living cells. Nat Methods
7:973–975. https://doi.org/10.1038/nmeth.
1524
10. Levskaya A, Weiner OD, Lim WA, Voigt CA
(2010) Spatiotemporal control of cell signalling using a light-switchable protein interaction. Nature 461:1–5. https://doi.org/10.
1038/nature08446
11. Guntas G, Hallett RA, Zimmerman SP,
Williams T, Yumerefendi H, Bear JE, Kuhlman
B (2015) Engineering an improved lightinduced dimer (iLID) for controlling the localization and activity of signaling proteins. Proc
Natl Acad Sci 112:112–117. https://doi.org/
10.1073/pnas.1417910112
12. Toettcher JE, Voigt CA, Weiner OD, Lim WA
(2011) The promise of optogenetics in cell
biology: interrogating molecular circuits in
space and time. Nat Methods 8:35–38.
https://doi.org/10.1038/nmeth.f.326
13. Valon L, Etoc F, Remorino A, Di Pietro F,
Morin X, Dahan M, Coppey M, di Pietro F,
Morin X, Dahan M, Coppey M (2015) Predictive spatiotemporal manipulation of signaling
perturbations using optogenetics. Biophys J
109:1785–1797. https://doi.org/10.1016/j.
bpj.2015.08.042
14. de Beco S, Vaidz ˇiulyte ˙ K, Manzi J, Dalier F, di
Federico F, Cornilleau G, Dahan M,
Coppey M, De Beco S, Manzi J, Dalier F,
Cornilleau G, Dahan M, Coppey M (2018)
Optogenetic dissection of Rac1 and Cdc42
gradient shaping. Nat Commun 9:1–13.
https://doi.org/10.1038/s41467-01807286-8
15. Valon L, Marı ´n-Llaurado ´ A, Wyatt T,
Charras G, Trepat X, Marin-Llaurado A,
Wyatt T, Charras G, Trepat X (2017) Optogenetic control of cellular forces and mechanotransduction. Nat Commun 8:14396. https://
doi.org/10.1038/ncomms14396
16. Lee S, Park H, Kyung T, Kim NY, Kim S,
Kim J, Do Heo W (2014) Reversible protein
inactivation by optogenetic trapping in cells.
Nat Methods 11:633–636. https://doi.org/
10.1038/nmeth.2940
17. Taslimi A, Vrana JD, Chen D, Borinskaya S,
Mayer BJ, Kennedy MJ, Tucker CL (2014) An
optimized optogenetic clustering tool for
probing protein interaction and function. Nat
Commun 5:4925. https://doi.org/10.1038/
ncomms5925
18. Grusch M, Schelch K, Riedler R, Reichhart E,
Differ C, Berger W, Ingle ´s-Prieto A ´ , Janovjak
H (2014) Spatio-temporally precise activation
of engineered receptor tyrosine kinases by
light. EMBO J 33:1713–1726. https://doi.
org/10.15252/embj.201387695
19. Bugaj LJ, Spelke DP, Mesuda CK, Varedi M,
Kane RS, Schaffer DV (2015) Regulation of
endogenous transmembrane receptors through
optogenetic Cry2 clustering. Nat Commun
6:6898.
https://doi.org/10.1038/
ncomms7898
20. Zhou XX, Fan LZ, Li P, Lin MZ (2017) Optical control of cell signaling by single-chain
photoswitchable kinases. Science 355:836–842
21. Leopold AV, Chernov KG, Verkhusha VV
(2018) Optogenetically controlled protein
kinases for regulation of cellular signaling.
Chem Soc Rev 47:2454–2484. https://doi.
org/10.1039/c7cs00404d
22. Strickland D, Lin Y, Wagner E, Hope CM,
Zayner J, Antoniou C, Sosnick TR, Weiss EL,
Glotzer M (2012) TULIPs: tunable, lightcontrolled interacting protein tags for cell biology. Nat Methods 9:379–384. https://doi.
org/10.1038/nmeth.1904
23. Hallett RA, Zimmerman SP, Yumerefendi H,
Bear JE, Kuhlman B (2016) Correlating
in vitro and in vivo activities of light-inducible
dimers: a cellular Optogenetics guide. ACS
Synth Biol 5:53–64. https://doi.org/10.
1021/acssynbio.5b00119
24. Filonov GS, Piatkevich KD, Ting L-M,
Zhang J, Kim K, Verkhusha VV (2011) Bright
and stable near-infrared fluorescent protein for
in vivo imaging. Nat Biotechnol 29:757–761.
https://doi.org/10.1038/nbt.1918
Control of Cell Migration Using Optogenetics
425