Localized cell death focuses mechanical forces during 3D patterning in a biofilm

Edited by Herbert Levine, University of California at San Diego, La Jolla, CA, and approved August 27, 2012 (received for review July 19, 2012)
September 24, 2012
109 (46) 18891-18896
Commentary
Turning death into creative force during biofilm engineering
Daniel Schultz, José N. Onuchic, Eshel Ben-Jacob

Abstract

From microbial biofilm communities to multicellular organisms, 3D macroscopic structures develop through poorly understood interplay between cellular processes and mechanical forces. Investigating wrinkled biofilms of Bacillus subtilis, we discovered a pattern of localized cell death that spatially focuses mechanical forces, and thereby initiates wrinkle formation. Deletion of genes implicated in biofilm development, together with mathematical modeling, revealed that ECM production underlies the localization of cell death. Simultaneously with cell death, we quantitatively measured mechanical stiffness and movement in WT and mutant biofilms. Results suggest that localized cell death provides an outlet for lateral compressive forces, thereby promoting vertical mechanical buckling, which subsequently leads to wrinkle formation. Guided by these findings, we were able to generate artificial wrinkle patterns within biofilms. Formation of 3D structures facilitated by cell death may underlie self-organization in other developmental systems, and could enable engineering of macroscopic structures from cell populations.

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Acknowledgments

We thank Drs. M. Heinemann, M. Lehrman, S. Lockless, M. Rosen, R. Ranganathan, K. Süel, and D. Sprinzak and members of the G.M.S. laboratory for comments on the manuscript; Drs. W. Winkler, R. Kolter, and K. Pogliano for kindly providing bacterial strains; and H. Wu for analyzing time-lapse images. H.L. acknowledges funding from National Science Foundation Grants DMR-0907291, CMMI-1031829, and 1132174 and National Institutes of Health Grants 1 R01 EB013212 and 1 R01 DC011585. J.G.O. acknowledges funding from Grant FIS2009-13360 from the Spanish Ministry of Economy and Competitiveness and the Institució Catalana de Recerca i Estudis Avançats Academia Programme. This research was funded by National Institutes of Health National Institute of General Medical Sciences Grant R01 GM088428 and James S. McDonnell Foundation Grant 220020141 (both to G.M.S.).

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Information & Authors

Information

Published in

Go to Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences
Vol. 109 | No. 46
November 13, 2012
PubMed: 23012477

Classifications

Submission history

Published online: September 24, 2012
Published in issue: November 13, 2012

Keywords

  1. pattern formation
  2. self-assembly
  3. systems dynamics

Acknowledgments

We thank Drs. M. Heinemann, M. Lehrman, S. Lockless, M. Rosen, R. Ranganathan, K. Süel, and D. Sprinzak and members of the G.M.S. laboratory for comments on the manuscript; Drs. W. Winkler, R. Kolter, and K. Pogliano for kindly providing bacterial strains; and H. Wu for analyzing time-lapse images. H.L. acknowledges funding from National Science Foundation Grants DMR-0907291, CMMI-1031829, and 1132174 and National Institutes of Health Grants 1 R01 EB013212 and 1 R01 DC011585. J.G.O. acknowledges funding from Grant FIS2009-13360 from the Spanish Ministry of Economy and Competitiveness and the Institució Catalana de Recerca i Estudis Avançats Academia Programme. This research was funded by National Institutes of Health National Institute of General Medical Sciences Grant R01 GM088428 and James S. McDonnell Foundation Grant 220020141 (both to G.M.S.).

Notes

*This Direct Submission article had a prearranged editor.
See Commentary on page 18633.

Authors

Affiliations

Munehiro Asally
Section of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093;
Mark Kittisopikul
Section of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093;
Department of Pharmacology and
Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390;
Pau Rué
Departament de Física i Enginyeria Nuclear, Universitat Politècnica de Catalunya, E-08222 Terrassa, Spain;
Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain; and
Yingjie Du
Department of Mechanical Engineering, University of Texas at Dallas, Richardson, TX 75080
Zhenxing Hu
Department of Mechanical Engineering, University of Texas at Dallas, Richardson, TX 75080
Tolga Çağatay
Department of Pharmacology and
Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390;
Andra B. Robinson
Department of Pharmacology and
Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390;
Hongbing Lu
Department of Mechanical Engineering, University of Texas at Dallas, Richardson, TX 75080
Jordi Garcia-Ojalvo
Departament de Física i Enginyeria Nuclear, Universitat Politècnica de Catalunya, E-08222 Terrassa, Spain;
Department of Experimental and Health Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain; and
Gürol M. Süel1 [email protected]
Section of Molecular Biology, Division of Biological Sciences, University of California at San Diego, La Jolla, CA 92093;

Notes

1
To whom correspondence should be addressed. E-mail: [email protected].
Author contributions: M.A., M.K., P.R., J.G.-O., and G.M.S. designed research; M.A., P.R., Y.D., Z.H., and A.B.R. performed research; M.A., M.K., P.R., T.Ç., and J.G.-O. contributed new reagents/analytic tools; M.A., M.K., Y.D., Z.H., H.L., and G.M.S. analyzed data; and M.A., J.G.-O., and G.M.S. wrote the paper.

Competing Interests

The authors declare no conflict of interest.

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    Localized cell death focuses mechanical forces during 3D patterning in a biofilm
    Proceedings of the National Academy of Sciences
    • Vol. 109
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    • pp. 18627-19033

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