Collective motion conceals fitness differences in crowded cellular populations


Many cellular populations are tightly packed, such as microbial colonies and biofilms, or tissues and tumours in multicellular organisms. The movement of one cell in these crowded assemblages requires motion of others, so that cell displacements are correlated over many cell diameters. Whenever movement is important for survival or growth, these correlated rearrangements could couple the evolutionary fate of different lineages. However, little is known about the interplay between mechanical forces and evolution in dense cellular populations. Here, by tracking slower-growing clones at the expanding edge of yeast colonies, we show that the collective motion of cells prevents costly mutations from being weeded out rapidly. Joint pushing by neighbouring cells generates correlated movements that suppress the differential displacements required for selection to act. This mechanical screening of fitness differences allows slower-growing mutants to leave more descendants than expected under non-mechanical models, thereby increasing their chance for evolutionary rescue. Our work suggests that, in crowded populations, cells cooperate with surrounding neighbours through inevitable mechanical interactions. This effect has to be considered when predicting evolutionary outcomes, such as the emergence of drug resistance or cancer evolution.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Slower-growing clones persist at the front of expanding yeast colonies.
Fig. 2: Delayed extinction can be described via an effective surface tension.
Fig. 3: Effective surface tension emerges in mechanical simulations from purely physical cell–cell interactions.
Fig. 4: Slow purging of costly drug-resistant mutations can lead to resurgent growth on drug application.
Fig. 5: Fitness screening affects faster-growing mutants and is independent of cell morphology.

Data availability

Imaging data used in this study are available at


  1. 1.

    Bertet, C., Sulak, L. & Lecuit, T. Myosin-dependent junction remodelling controls planar cell intercalation and axis elongation. Nature 429, 667–671 (2004).

    CAS  Article  Google Scholar 

  2. 2.

    Farhadifar, R., Röper, J.-C., Aigouy, B., Eaton, S. & Jülicher, F. The influence of cell mechanics, cell–cell interactions, and proliferation on epithelial packing. Curr. Biol. 17, 2095–2104 (2007).

    CAS  Article  Google Scholar 

  3. 3.

    Excoffier, L. & Ray, N. Surfing during population expansions promotes genetic revolutions and structuration. Trends Ecol. Evol. 23, 347–351 (2008).

    Article  Google Scholar 

  4. 4.

    Gralka, M. et al. Allele surfing promotes microbial adaptation from standing variation. Ecol. Lett. 19, 889–898 (2016).

    Article  Google Scholar 

  5. 5.

    Hallatschek, O., Hersen, P., Ramanathan, S. & Nelson, D. R. Genetic drift at expanding frontiers promotes gene segregation. Proc. Natl Acad. Sci. USA 104, 19926–19930 (2007).

    CAS  Article  Google Scholar 

  6. 6.

    Korolev, K. S., Avlund, M., Hallatschek, O. & Nelson, D. R. Genetic demixing and evolution in linear stepping stone models. Rev. Mod. Phys. 82, 1691–1718 (2010).

    CAS  Article  Google Scholar 

  7. 7.

    Farrell, F. D. C., Hallatschek, O., Marenduzzo, D. & Waclaw, B. Mechanically driven growth of quasi-two-dimensional microbial colonies. Phys. Rev. Lett. 111, 168101 (2013).

    CAS  Article  Google Scholar 

  8. 8.

    Farrell, F. D., Gralka, M., Hallatschek, O. & Waclaw, B. Mechanical interactions in bacterial colonies and the surfing probability of beneficial mutations. J. R. Soc. Interface 14, 20170073 (2017).

    Article  Google Scholar 

  9. 9.

    Fusco, D., Gralka, M., Kayser, J., Anderson, A. & Hallatschek, O. Excess of mutational jackpot events in expanding populations revealed by spatial Luria–Delbrück experiments. Nat. Commun. 7, 12760 (2016).

    CAS  Article  Google Scholar 

  10. 10.

    Lavrentovich, M. O., Korolev, K. S. & Nelson, D. R. Radial Domany–Kinzel models with mutation and selection. Phys. Rev. E 87, 012103 (2013).

    Article  Google Scholar 

  11. 11.

    Meunier, J.-R. & Choder, M. Saccharomyces cerevisiae colony growth and ageing: biphasic growth accompanied by changes in gene expression. Yeast 15, 1159–1169 (1999).

    CAS  Article  Google Scholar 

  12. 12.

    Váchová, L. & Palková, Z. How structured yeast multicellular communities live, age and die? FEMS Yeast Res. 18, foy033 (2018).

    Article  Google Scholar 

  13. 13.

    Hallatschek, O. & Nelson, D. R. Life at the front of an expanding population. Evolution 64, 193–206 (2010).

    Article  Google Scholar 

  14. 14.

    Korolev, K. S. et al. Selective sweeps in growing microbial colonies. Phys. Biol. 9, 026008 (2012).

    Article  Google Scholar 

  15. 15.

    Van Dyken, J. D., Müller, M. J. I., Mack, K. M. L. & Desai, M. M. Spatial population expansion promotes the evolution of cooperation in an experimental prisoners dilemma. Curr. Biol. 23, 919–923 (2013).

    CAS  Article  Google Scholar 

  16. 16.

    Baym, M. et al. Spatiotemporal microbial evolution on antibiotic landscapes. Science 353, 1147–1151 (2016).

    CAS  Article  Google Scholar 

  17. 17.

    Nadell, C. D., Foster, K. R. & Xavier, J. B. Emergence of spatial structure in cell groups and the evolution of cooperation. PLoS Comput. Biol. 6, e1000716 (2010).

    Article  Google Scholar 

  18. 18.

    Müller, M. J. I., Neugeboren, B. I., Nelson, D. R. & Murray, A. W. Genetic drift opposes mutualism during spatial population expansion. Proc. Natl Acad. Sci. USA 111, 1037–1042 (2014).

    Article  Google Scholar 

  19. 19.

    Peischl, S., Dupanloup, I., Kirkpatrick, M. & Excoffier, L. On the accumulation of deleterious mutations during range expansions. Mol. Ecol. 22, 5972–5982 (2013).

    CAS  Article  Google Scholar 

  20. 20.

    Lamprecht, S. et al. Multicolor lineage tracing reveals clonal architecture and dynamics in colon cancer. Nat. Commun. 8, 1406 (2017).

    Article  Google Scholar 

  21. 21.

    Asally, M. et al. Localized cell death focuses mechanical forces during 3D patterning in a biofilm. Proc. Natl Acad. Sci. USA 109, 18891–18896 (2012).

    CAS  Article  Google Scholar 

  22. 22.

    Smith, W. P. J. et al. Cell morphology drives spatial patterning in microbial communities. Proc. Natl Acad. Sci. USA 114, E280–E286 (2017).

    CAS  Article  Google Scholar 

  23. 23.

    Yan, J., Sharo, A. G., Stone, H. A., Wingreen, N. S. & Bassler, B. L. Vibrio cholerae biofilm growth program and architecture revealed by single-cell live imaging. Proc. Natl Acad. Sci. USA 113, E5337–E5343 (2016).

    CAS  Article  Google Scholar 

  24. 24.

    Vopálenská, I., Hůlková, M., Janderová, B. & Palková, Z. The morphology of Saccharomyces cerevisiae colonies is affected by cell adhesion and the budding pattern. Res. Microbiol. 156, 921–931 (2005).

    Article  Google Scholar 

  25. 25.

    Korolev, K. S., Xavier, J. B., Nelson, D. R. & Foster, K. R. A quantitative test of population genetics using spatiogenetic patterns in bacterial colonies. Am. Nat. 178, 538–552 (2011).

    Article  Google Scholar 

  26. 26.

    Lavrentovich, M. O., Wahl, M. E., Nelson, D. R. & Murray, A. W. Spatially constrained growth enhances conversional meltdown. Biophys. J. 110, 2800–2808 (2016).

    CAS  Article  Google Scholar 

  27. 27.

    Wahl, M. E. & Murray, A. W. Multicellularity makes somatic differentiation evolutionarily stable. Proc. Natl Acad. Sci. USA 113, 8362–8367 (2016).

    CAS  Article  Google Scholar 

  28. 28.

    Bidan, C. M. et al. How linear tension converts to curvature: geometric control of bone tissue growth. PLoS ONE 7, e36336 (2012).

    CAS  Article  Google Scholar 

  29. 29.

    Lecuit, T. & Lenne, P.-F. Cell surface mechanics and the control of cell shape, tissue patterns and morphogenesis. Nat. Rev. Mol. Cell Biol. 8, 633–644 (2007).

    CAS  Article  Google Scholar 

  30. 30.

    Nguyen, B., Upadhyaya, A., van Oudenaarden, A. & Brenner, M. P. Elastic instability in growing yeast colonies. Biophys. J. 86, 2740–2747 (2004).

    CAS  Article  Google Scholar 

  31. 31.

    Wang, X., Stone, H. A. & Golestanian, R. Shape of the growing front of biofilms. New J. Phys. 19, 125007 (2017).

    Article  Google Scholar 

  32. 32.

    Kardar, M., Parisi, G. & Zhang, Y.-C. Dynamic scaling of growing interfaces. Phys. Rev. Lett. 56, 889–892 (1986).

    CAS  Article  Google Scholar 

  33. 33.

    Giometto, A., Nelson, D. R. & Murray, A. W. Physical interactions reduce the power of natural selection in growing yeast colonies. Proc. Natl Acad. Sci. USA 115, 11448–11453 (2018).

    CAS  Article  Google Scholar 

  34. 34.

    Andersson, D. I. & Hughes, D. Antibiotic resistance and its cost: is it possible to reverse resistance? Nat. Rev. Microbiol. 8, 260–271 (2010).

    CAS  Article  Google Scholar 

  35. 35.

    Gagneux, S. et al. The competitive cost of antibiotic resistance in Mycobacterium tuberculosis. Science 312, 1944–1946 (2006).

    CAS  Article  Google Scholar 

  36. 36.

    Bell, G. & Gonzalez, A. Evolutionary rescue can prevent extinction following environmental change. Ecol. Lett. 12, 942–948 (2009).

    Article  Google Scholar 

  37. 37.

    Carlson, S. M., Cunningham, C. J. & Westley, P. A. H. Evolutionary rescue in a changing world. Trends Ecol. Evol. 29, 521–530 (2014).

    Article  Google Scholar 

  38. 38.

    Weinstein, B. T., Lavrentovich, M. O., Möbius, W., Murray, A. W. & Nelson, D. R. Genetic drift and selection in many-allele range expansions. PLoS Comput. Biol. 13, e1005866 (2017).

    Article  Google Scholar 

  39. 39.

    Excoffier, L., Foll, M. & Petit, R. J. Genetic consequences of range expansions. Annu. Rev. Ecol. Evol. Syst. 40, 481–501 (2009).

    Article  Google Scholar 

  40. 40.

    Weissman, D. B., Desai, M. M., Fisher, D. S. & Feldman, M. W. The rate at which asexual populations cross fitness valleys. Theor. Popul. Biol. 75, 286–300 (2009).

    Article  Google Scholar 

  41. 41.

    Golding, I., Kozlovsky, Y., Cohen, I. & Ben-Jacob, E. Studies of bacterial branching growth using reaction–diffusion models for colonial development. Physica A Stat. Mech. Appl. 260, 510–554 (1998).

    CAS  Article  Google Scholar 

  42. 42.

    Ke, W.-J., Hueh, Y.-H., Cheng, Y.-C., Wu, C.-C. & Liu, S.-T. Water surface tension modulates the swarming mechanics of Bacillus subtilis. Front. Microbiol. 6, 1017 (2015).

    PubMed  PubMed Central  Google Scholar 

  43. 43.

    Klapper, I. & Dockery, J. Finger formation in biofilm layers. SIAM J. Appl. Math. 62, 853–869 (2002).

    Article  Google Scholar 

  44. 44.

    Matsushita, M. & Fujikawa, H. Diffusion-limited growth in bacterial colony formation. Physica A Stat. Mech. Appl. 168, 498–506 (1990).

    CAS  Article  Google Scholar 

  45. 45.

    Foty, R. A. & Steinberg, M. S. The differential adhesion hypothesis: a direct evaluation. Dev. Biol. 6, 255–263 (2005).

    Article  Google Scholar 

  46. 46.

    Amack, J. D. & Manning, M. L. Knowing the boundaries: extending the differential adhesion hypothesis in embryonic cell sorting. Science 338, 212–215 (2012).

    CAS  Article  Google Scholar 

  47. 47.

    Manning, M. L., Foty, R. A., Steinberg, M. S. & Schoetz, E.-M. Coaction of intercellular adhesion and cortical tension specifies tissue surface tension. Proc. Natl Acad. Sci. USA 107, 12517–12522 (2010).

    CAS  Article  Google Scholar 

  48. 48.

    Mertz, A. F. et al. Scaling of traction forces with the size of cohesive cell colonies. Phys. Rev. Lett. 108, 198101 (2012).

    Article  Google Scholar 

  49. 49.

    Friedman, J. & Gore, J. Ecological systems biology: the dynamics of interacting populations. Curr. Opin. Syst. Biol. 1, 114–121 (2017).

    Article  Google Scholar 

  50. 50.

    Nadell, C. D., Drescher, K. & Foster, K. R. Spatial structure, cooperation and competition in biofilms. Nat. Rev. Microbiol. 14, 589–600 (2016).

    CAS  Article  Google Scholar 

  51. 51.

    Korolev, K. S., Xavier, J. B. & Gore, J. Turning ecology and evolution against cancer. Nat. Rev. Cancer 14, 371–380 (2014).

    CAS  Article  Google Scholar 

  52. 52.

    Lambert, G. et al. An analogy between the evolution of drug resistance in bacterial communities and malignant tissues. Nat. Rev. Cancer 11, 375–382 (2011).

    CAS  Article  Google Scholar 

  53. 53.

    Waters, J. M., Fraser, C. I. & Hewitt, G. M. Founder takes all: density-dependent processes structure biodiversity. Trends Ecol. Evol. 28, 78–85 (2013).

    Article  Google Scholar 

  54. 54.

    Bosshard, L. et al. Accumulation of deleterious mutations during bacterial range expansions. Genetics 207, 669–684 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. 55.

    Otwinowski, J. & Krug, J. Clonal interference and Muller’s ratchet in spatial habitats. Phys. Biol. 11, 056003 (2014).

    Article  Google Scholar 

  56. 56.

    Martens, E. A., Kostadinov, R., Maley, C. C. & Hallatschek, O. Spatial structure increases the waiting time for cancer. New J. Phys. 13, 115014 (2011).

    Article  Google Scholar 

  57. 57.

    Yan, J., Nadell, C. D., Stone, H. A., Wingreen, N. S. & Bassler, B. L. Extracellular-matrix-mediated osmotic pressure drives Vibrio cholerae biofilm expansion and cheater exclusion. Nat. Commun. 8, 327 (2017).

    Article  Google Scholar 

  58. 58.

    Lambert, G. & Kussell, E. Memory and fitness optimization of bacteria under fluctuating environments. PLoS Genet. 10, e1004556 (2014).

    Article  Google Scholar 

  59. 59.

    Lindsey, H. A., Gallie, J., Taylor, S. & Kerr, B. Evolutionary rescue from extinction is contingent on a lower rate of environmental change. Nature 494, 463–467 (2013).

    CAS  Article  Google Scholar 

  60. 60.

    Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676–682 (2012).

    CAS  Article  Google Scholar 

  61. 61.

    Tseng, Q. et al. Spatial organization of the extracellular matrix regulates cell–cell junction positioning. Proc. Natl Acad. Sci. USA 109, 1506–1511 (2012).

    CAS  Article  Google Scholar 

  62. 62.

    Delarue, M. et al. Self-driven jamming in growing microbial populations. Nat. Phys. 12, 762–766 (2016).

    CAS  Article  Google Scholar 

  63. 63.

    Schreck, C. F., Xu, N. & O’Hern, C. S. A comparison of jamming behavior in systems composed of dimer- and ellipse-shaped particles. Soft Matter 6, 2960–2969 (2010).

    CAS  Article  Google Scholar 

  64. 64.

    Eden, M. A two-dimensional growth process. Dynam. Fractal Surf. 4, 223–239 (1961).

    Google Scholar 

Download references


Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under award R01GM115851, a National Science Foundation CAREER Award (#1555330), a Simons Investigator award from the Simons Foundation (#327934), the National Energy Research Scientific Computing Center, a US Department of Energy Office of Science User Facility operated under contract number DE-AC02-05CH11231, and the Berkeley Research Computing programme at the University of California, Berkeley. J.K. acknowledges a research scholarship (KA 4486/1-1) awarded by the German Research Foundation. The authors thank B. Good, J. Paulose, M.-C. Duvernoy and S. Martis for vital discussions, and the group of J. Rine for invaluable insights on yeast genetics.

Author information




J.K., C.F.S. and O.H. conceived and designed the study. J.K. and M.G. carried out and analysed the experiments. C.F.S., M.G., D.F. and J.K. performed and evaluated the simulations. J.K., C.F.S., M.G., D.F. and O.H. discussed and interpreted the results. J.K., C.F.S. and O.H. wrote the manuscript.

Corresponding author

Correspondence to Oskar Hallatschek.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary Text, Video Legends and Fig. 1–21.

Reporting Summary

Supplementary Video 1

Time lapse series of a shrinking wide-mutant sector in a linear front.

Supplementary Video 2

Simulation of a shrinking mutant clone.

Supplementary Video 3

Single cell tracking at a moderately curved front.

Supplementary Video 4

Single cell tracking at a highly curved front.

Supplementary Video 5

Single cell tracking of front cells starting at birth.

Supplementary Video 6

Simulation of expanding, budding yeast cell population.

Supplementary Video 7

Fate of a slower growing clone after expulsion from the front.

Supplementary Video 8

Resurgent growth of a persisting mutant sector after drug application.

Supplementary Video 9

Single cell tracking at the mutant–wild-type boundary.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kayser, J., Schreck, C.F., Gralka, M. et al. Collective motion conceals fitness differences in crowded cellular populations. Nat Ecol Evol 3, 125–134 (2019).

Download citation

Further reading


Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing