Cell-cycle progression is regulated by numerous intricate endogenous mechanisms, among which intracellular forces and protein motors are central players. Although it seems unlikely that it is possible to speed up this molecular machinery by applying tiny external forces to the cell, we show that magnetic forcing of magnetosensitive bacteria reduces the duration of the mitotic phase. In such bacteria, the coupling of the cell cycle to the splitting of chains of biogenic magnetic nanoparticles (BMNs) provides a biological realization of such forcing. Using a static gradient magnetic field of a special spatial configuration, in probiotic bacteria E. coli Nissle 1917, we shortened the duration of the mitotic phase and thereby accelerated cell division. Thus, focused magnetic gradient forces exerted on the BMN chains allowed us to intervene in the processes of division and growth of bacteria. The proposed magnetic-based cell division regulation strategy can improve the efficiency of microbial cell factories and medical applications of magnetosensitive bacteria.

Faculty of Biotechnology and Biotechnics National Technical University of Ukraine Igor Sikorsky Kyiv Polytechnic Institute 03056 Kyiv Ukraine

Faculty of Physics and Mathematics National Technical University of Ukraine Igor Sikorsky Kyiv Polytechnic Institute 03056 Kyiv Ukraine

Institute of Magnetism of the National Academy of Sciences of Ukraine and Ministry of Education and Science of Ukraine 03142 Kyiv Ukraine

Institute of Physics of the Czech Academy of Sciences Na Slovance 1999 2 182 00 Prague Czech Republic

International Magnetobiology Frontier Research Center Science Island Hefei 230000 China

Zobrazit více v PubMed

Wang J.D., Levin P.A. Metabolism. Cell Growth and the Bacterial Cell Cycle. Nat. Rev. Microbiol. 2009;7:822. doi: 10.1038/nrmicro2202. PubMed DOI PMC

Schaechter M., MaalOe O., Kjeldgaard N.O. Dependency on Medium and Temperature of Cell Size and Chemical Composition during Balanced Growth of Salmonella Typhimurium. J. Gen. Microbiol. 1958;19:592. doi: 10.1099/00221287-19-3-592. PubMed DOI

Ayala M.R., Syrovets T., Hafner S., Zablotskii V., Dejneka A., Simmet T. Spatiotemporal Magnetic Fields Enhance Cytosolic Ca2+ Levels and Induce Actin Polymerization via Activation of Voltage-Gated Sodium Channels in Skeletal Muscle Cells. Biomaterials. 2018;163:174. doi: 10.1016/j.biomaterials.2018.02.031. PubMed DOI

Zablotskii V., Lunov O., Novotná B., Churpita O., Trošan P., Holáň V., Syková E., Dejneka A., Kubinová Š. Down-Regulation of Adipogenesis of Mesenchymal Stem Cells by Oscillating High-Gradient Magnetic Fields and Mechanical Vibration. Appl. Phys. Lett. 2014;105:103702. doi: 10.1063/1.4895459. DOI

Zablotskii V., Polyakova T., Dejneka A. Cells in the Non-Uniform Magnetic World: How Cells Respond to High-Gradient Magnetic Fields. BioEssays. 2018;40:1800017. doi: 10.1002/bies.201800017. PubMed DOI

Wosik J., Chen W., Qin K., Ghobrial R.M., Kubiak J.Z., Kloc M. Magnetic Field Changes Macrophage Phenotype. Biophys. J. 2018;114:2001. doi: 10.1016/j.bpj.2018.03.002. PubMed DOI PMC

Zablotskii V., Polyakova T., Lunov O., Dejneka A. How a High-Gradient Magnetic Field Could Affect Cell Life. Sci. Rep. 2016;6:37407. doi: 10.1038/srep37407. PubMed DOI PMC

Strahl H., Hamoen L.W. Membrane Potential Is Important for Bacterial Cell Division. Proc. Natl. Acad. Sci. USA. 2010;107:12281. doi: 10.1073/pnas.1005485107. PubMed DOI PMC

Colin A., Micali G., Faure L., Lagomarsino M.C., van Teeffelen S. Two Different Cell-Cycle Processes Determine the Timing of Cell Division in Escherichia Coli. Elife. 2021;10:e67495. doi: 10.7554/eLife.67495. PubMed DOI PMC

CBrangwynne P., Koenderink G.H., MacKintosh F.C., Weitz D.A. Nonequilibrium Microtubule Fluctuations in a Model Cytoskeleton. Phys. Rev. Lett. 2008;100:118104. doi: 10.1103/PhysRevLett.100.118104. PubMed DOI

Zablotskii V., Lunov O., Kubinova S., Polyakova T., Sykova E., Dejneka A. Effects of High-Gradient Magnetic Fields on Living Cell Machinery. J. Phys. D Appl. Phys. 2016;49:493003. doi: 10.1088/0022-3727/49/49/493003. DOI

KCylke C., Banerjee S. Accelerating Growth and Stochastic Shape Dynamics in Rod-like Bacteria. BioRxiv. 2022 doi: 10.1101/2022.05.21.492931. DOI

Biswas K., Brenner N. Cell-Division Time Statistics from Stochastic Exponential Threshold-Crossing. BioRxiv. 2022:10.1101/20. doi: 10.1101/2022.08.21.504683. DOI

Zhang L., Hou Y., Li Z., Ji X., Wang Z., Wang H., Tian X., Yu F., Yang Z., Pi L., et al. 27 T Ultra-High Static Magnetic Field Changes Orientation and Morphology of Mitotic Spindles in Human Cells. Elife. 2017;6:e22911. doi: 10.7554/eLife.22911. PubMed DOI PMC

Tseng P., Judy J.W., Di Carlo D. Magnetic Nanoparticle–Mediated Massively Parallel Mechanical Modulation of Single-Cell Behavior. Nat. Methods. 2012;9:1113. doi: 10.1038/nmeth.2210. PubMed DOI PMC

Mendelson N.H. Bacterial Growth and Division: Genes, Structures, Forces, and Clocks. Microbiol. Rev. 1982;46:341–375. doi: 10.1128/mr.46.3.341-375.1982. PubMed DOI PMC

Blakemore R. Magnetotactic Bacteria. Science. 1975;190:377. doi: 10.1126/science.170679. PubMed DOI

Kobayashi A., Yamamoto N., Kirschvink J. Studies of Inorganic Crystals in Biological Tissue: Magnetic in Human Tumor. J. Jpn. Soc. Powder Powder Metall. 1997;44:294. doi: 10.2497/jjspm.44.294. DOI

Gorobets O., Gorobets S., Koralewski M. Physiological Origin of Biogenic Magnetic Nanoparticles in Health and Disease: From Bacteria to Humans. Int. J. Nanomed. 2017;12:4371. doi: 10.2147/IJN.S130565. PubMed DOI PMC

Kirschvink J.L. Magnetite Biomineralization and Geomagnetic Sensitivity in Higher Animals: An Update and Recommendations for Future Study. Bioelectromagnetics. 1989;10:239–259. doi: 10.1002/bem.2250100304. PubMed DOI

Kirschvink J.L., Gould J.L. Biogenic Magnetite as a Basis for Magnetic Field Detection in Animals. Biosystems. 1981;13:181–201. doi: 10.1016/0303-2647(81)90060-5. PubMed DOI

Kirschvink J. Magnetite-Based Magnetoreception. Curr. Opin. Neurobiol. 2001;11:462. doi: 10.1016/S0959-4388(00)00235-X. PubMed DOI

JKirschvink L., Douglas S.J., Bruce J.M. Magnetite Biomineralization and Magnetoreception in Organisms a New Biomagnetism. Plenum Press; New York, NY, USA: 1985.

Bauer G.B., Fuller M., Perry A., Dunn J.R., Zoeger J. Magnetoreception and Biomineralization of Magnetite in Cetaceans. Springer; Boston, MA, USA: 1985.

Gorobets S.V., Yu G.O., Demianenko I.V., Nikolaenko R.N. Self-Organization of Magnetite Nanoparticles in Providing Saccharomyces Cerevisiae Yeasts with Magnetic Properties. J. Magn. Magn. Mater. 2013;337:53–57. doi: 10.1016/j.jmmm.2013.01.004. DOI

Gorobets S.V., Gorobets O.Y., Chyzh Y.M., Sivenok D.V. Magnetic Dipole Interaction of Endogenous Magnetic Nanoparticles with Magnetoliposomes for Targeted Drug Delivery. Biophysics. 2013;58:379. doi: 10.1134/S000635091303007X. PubMed DOI

Bazylinski D.A., Frankel R.B. Magnetosome Formation in Prokaryotes. Nat. Rev. Microbiol. 2004;2:217. doi: 10.1038/nrmicro842. PubMed DOI

Arakaki A., Nakazawa H., Nemoto M., Mori T., Matsunaga T. Formation of Magnetite by Bacteria and Its Application. J. R. Soc. Interface. 2008;5:977–999. doi: 10.1098/rsif.2008.0170. PubMed DOI PMC

Taoka A., Asada R., Wu L.-F., Fukumori Y. Polymerization of the Actin-Like Protein MamK, Which Is Associated with Magnetosomes. J. Bacteriol. 2007;189:8737. doi: 10.1128/JB.00899-07. PubMed DOI PMC

Vainshtein M., Suzina N., Kudryashova E., Ariskina E. New Magnet-Sensitive Structures in Bacterial and Archaeal Cells. Biol. Cell. 2002;94:29. doi: 10.1016/S0248-4900(02)01179-6. PubMed DOI

Kirschvink J.L., Kobayashi-Kirschvink A., Diaz-Ricci J.C., Kirschvink S.J. Magnetite in Human Tissues: A Mechanism for the Biological Effects of Weak ELF Magnetic Fields. Bioelectromagnetics. 1992;13:101–113. doi: 10.1002/bem.2250130710. PubMed DOI

Staniland S.S., Moisescu C., Benning L.G. Cell Division in Magnetotactic Bacteria Splits Magnetosome Chain in Half. J. Basic Microbiol. 2010;50:392. doi: 10.1002/jobm.200900408. PubMed DOI

Schubbe S., Wurdemann C., Peplies J., Heyen U., Wawer C., Gluckner F.O., Schuler D. Transcriptional Organization and Regulation of Magnetosome Operons in Magnetospirillum Gryphiswaldense. Appl. Environ. Microbiol. 2006;72:5757. doi: 10.1128/AEM.00201-06. PubMed DOI PMC

Lohße A., Ullrich S., Katzmann E., Borg S., Wanner G., Richter M., Voigt B., Schweder T., Schu D. Functional Analysis of the Magnetosome Island in Magnetospirillum Gryphiswaldense: The MamAB Operon Is Sufficient for Magnetite Biomineralization. PLoS ONE. 2011;6:e25561. doi: 10.1371/journal.pone.0025561. PubMed DOI PMC

Gorobets S.V., Medviediev O.V., Gorobets O.Y., Ivanchenko A. Biogenic Magnetic Nanoparticles in Human Organs and Tissues. Prog. Biophys. Mol. Biol. 2018;135:49. doi: 10.1016/j.pbiomolbio.2018.01.010. PubMed DOI

Gorobets O.Y., Gorobets S.V., Sorokina L.V. Biomineralization and Synthesis of Biogenic Magnetic Nanoparticles and Magnetosensitive Inclusions in Microorganisms and Fungi. Funct. Mater. 2014;21:373. doi: 10.15407/fm21.04.427. DOI

Gorobets O.Y., Gorobets S.V., Gorobets Y.I. Dekker Encyclopedia of Nanoscience and Nanotechnology. 3rd ed. CRC Press; New York, NY, USA: 2014. Biogenic Magnetic Nanoparticles. Biomineralization in Prokaryotes and Eukaryotes; pp. 300–308.

Medviediev O., Gorobets O.Y., Gorobets S.V., Yadrykhins’Ky V.S. The Prediction of Biogenic Magnetic Nanoparticles Biomineralization in Human Tissues and Organs. J. Phys. Conf. Ser. 2017;903:012002. doi: 10.1088/1742-6596/903/1/012002. DOI

Van de Walle A., Sangnier A.P., Abou-Hassan A., Curcio A., Hémadi M., Menguy N., Lalatonne Y., Luciani N., Wilhelm C. Biosynthesis of Magnetic Nanoparticles from Nano-Degradation Products Revealed in Human Stem Cells. Proc. Natl. Acad. Sci. USA. 2019;116:4044. doi: 10.1073/pnas.1816792116. PubMed DOI PMC

Schüler D. Magnetoreception and Magnetosomes in Bacteria. Springer; Berlin/Heidelberg, Germany: New York, NY, USA: 2007.

Elkady A.S., Iskakova L., Zubarev A. On the Self-Assembly of Net-like Nanostructures in Ferrofluids. Phys. A Stat. Mech. Appl. 2015;428:257–265. doi: 10.1016/j.physa.2015.01.053. DOI

Gorobets S.V., Legenkii Y.A., Melnichuk I.A. Break-up of Ni Microparticle Clusters in a Magnetic Field. J. Magn. Magn. Mater. 2000;222:159. doi: 10.1016/S0304-8853(00)00522-9. DOI

Baryakhtar F.G., Gorobets Y.I., Kosachevski L.Y., Ilchishyn O.V., Hizhenkov P.K. Hexagonal Lattice of Cylindrical Magnetic Domains in Thin Films of a Ferrofluid. Magn. Gidrodin. 1981;3:120–123.

Gorobets S., Gorobets O., Magerman A., Gorobets Y., Sharay I. Biogenic Magnetic Nanoparticles in Plants. arXiv. 20191901.07212

Zhou Y., Han Y. Engineered Bacteria as Drug Delivery Vehicles: Principles and Prospects. Eng. Microbiol. 2022;2:100034. doi: 10.1016/j.engmic.2022.100034. DOI

Akolpoglu M.B., Alapan Y., Dogan N.O., Baltaci S.F., Yasa O., Tural G.A., Sitti M. Magnetically Steerable Bacterial Microrobots Moving in 3D Biological Matrices for Stimuli-Responsive Cargo Delivery. Sci. Adv. 2022;8:eabo6163. doi: 10.1126/sciadv.abo6163. PubMed DOI PMC

Aubry M., Wang W.-A., Guyodo Y., Delacou E., Guigner J.-M., Espeli O., Lebreton A., Guyot F., Gueroui Z. Engineering E. Coli for Magnetic Control and the Spatial Localization of Functions. ACS Synth. Biol. 2020;9:3030. doi: 10.1021/acssynbio.0c00286. PubMed DOI

Stritzker J., Weibel S., Hill P., Oelschlaeger T., Goebel W., Szalay A. Tumor-Specific Colonization, Tissue Distribution, and Gene Induction by Probiotic Escherichia Coli Nissle 1917 in Live Mice. Int. J. Med. Microbiol. 2007;297:151. doi: 10.1016/j.ijmm.2007.01.008. PubMed DOI

Zhang Y., Zhang Y., Xia L., Zhang X., Ding X., Yan F., Wu F. Escherichia Coli Nissle 1917 Targets and Restrains Mouse B16 Melanoma and 4T1 Breast Tumors through Expression of Azurin Protein. Appl. Environ. Microbiol. 2012;78:7603. doi: 10.1128/AEM.01390-12. PubMed DOI PMC

Westphal K., Leschner S., Jablonska J., Loessner H., Weiss S. Containment of Tumor-Colonizing Bacteria by Host Neutrophils. Cancer Res. 2008;68:2952. doi: 10.1158/0008-5472.CAN-07-2984. PubMed DOI

Sturm A., Rilling K., Baumgart D.C., Gargas K., Abou-Ghazale T., Raupach B., Eckert J., Schumann R.R., Enders C., Sonnenborn U., et al. Escherichia Coli Nissle 1917 Distinctively Modulates T-Cell Cycling and Expansion via Toll-Like Receptor 2 Signaling. Infect. Immun. 2005;73:1452. doi: 10.1128/IAI.73.3.1452-1465.2005. PubMed DOI PMC

Arribas B., Rodríguez-Cabezas M., Camuesco D., Comalada M., Bailón E., Utrilla P., Nieto A., Concha A., Zarzuelo A., Gálvez J. A Probiotic Strain of Escherichia Coli, Nissle 1917, given Orally Exerts Local and Systemic Anti-Inflammatory Effects in Lipopolysaccharide-Induced Sepsis in Mice. Br. J. Pharmacol. 2009;157:1024. doi: 10.1111/j.1476-5381.2009.00270.x. PubMed DOI PMC

Zhang Y., Ji W., He L., Chen Y., Ding X., Sun Y., Hu S., Yang H., Huang W., Zhang Y., et al. Coli Nissle 1917-Derived Minicells for Targeted Delivery of Chemotherapeutic Drug to Hypoxic Regions for Cancer Therapy. Theranostics. 2018;8:1690. doi: 10.7150/thno.21575. PubMed DOI PMC

Gwyddion: Scanning Probe Microscopy Data Visualisation and Analysis. [(accessed on 30 October 2022)]. Available online: https://sourceforge.net/projects/gwyddion/

NT_MDT, MFM General Concept. [(accessed on 30 October 2022)]. Available online: https://www.ntmdt-si.com/resources/spm-theory/theoretical-background-of-spm/2-scanning-force-microscopy--(sfm)/27-magnetic-force-microscopy-quantitative-results-treatment/271-mfm-general-concept.

Stover N.A., Cavalcanti A.R.O. Using NCBI BLAST. Curr. Protoc. Essent. Lab. Tech. 2014;8:11.1.1–11.1.35. doi: 10.1002/9780470089941.et1101s08. DOI

Hubert A., Schäfer R. Magnetic Domains: The Analysis of Magnetic Microstructures. Springer; New York, NY, USA: 1998.

Zablotskii V., Pastor J.M., Larumbe S., Pe J.I., Recarte V., Go C., Ha U., Schu W., Zborowski M. High-Field Gradient Permanent Micromagnets for Targeted Drug Delivery with Magnetic Nanoparticles. Volume 1311. American Institute of Physics; College Park, MD, USA: 2010. pp. 152–157.

Samofalov V.N., Belozorov D.P., Ravlik A.G. Strong Stray Fields in Systems of Giant Magnetic Anisotropy Magnets. Physics-Uspekhi. 2013;56:269. doi: 10.3367/UFNe.0183.201303e.0287. DOI

Nadkarni R., Barkley S., Fradin C. A Comparison of Methods to Measure the Magnetic Moment of Magnetotactic Bacteria through Analysis of Their Trajectories in External Magnetic Fields. PLoS ONE. 2013;8:e82064. doi: 10.1371/journal.pone.0082064. PubMed DOI PMC

Callaway E. How Bacteria Break a Magnet. Nature. 2011 doi: 10.1038/nature.2011.9659. DOI

Katzmann E., Müller F.D., Lang C., Messerer M., Winklhofer M., Plitzko J.M., Schüler D. Magnetosome Chains Are Recruited to Cellular Division Sites and Split by Asymmetric Septation. Mol. Microbiol. 2011;82:1316. doi: 10.1111/j.1365-2958.2011.07874.x. PubMed DOI

Sabass B., Koch M.D., Liu G., Stone H.A., Shaevitz J.W. Force Generation by Groups of Migrating Bacteria. Proc. Natl. Acad. Sci. USA. 2017;114:7266. doi: 10.1073/pnas.1621469114. PubMed DOI PMC

Dewachter L., Verstraeten N., Fauvart M., Michiels J. An Integrative View of Cell Cycle Control in Escherichia Coli. FEMS Microbiol. Rev. 2018;42:116. doi: 10.1093/femsre/fuy005. PubMed DOI

Michelsen O., de Mattos M.J.T., Jensen P.R., Hansen F.G. Precise Determinations of C and D Periods by Flow Cytometry in Escherichia Coli K-12 and B/R. Microbiology. 2003;149:1001. doi: 10.1099/mic.0.26058-0. PubMed DOI

Zwietering M.H., Jongenburger I., Rombouts F.M., van ’t Riet K. Modeling of the Bacterial Growth Curve. Appl. Environ. Microbiol. 1990;56:1875. doi: 10.1128/aem.56.6.1875-1881.1990. PubMed DOI PMC

You Z., Pearce D.J.G., Sengupta A., Giomi L. Geometry and Mechanics of Microdomains in Growing Bacterial Colonies. Phys. Rev. X. 2018;8:031065. doi: 10.1103/PhysRevX.8.031065. DOI

Panlilio M., Grilli J., Tallarico G., Iuliani I., Sclavi B., Cicuta P., Lagomarsino M.C. Threshold Accumulation of a Constitutive Protein Explains E. Coli Cell-Division Behavior in Nutrient Upshifts. Proc. Natl. Acad. Sci. USA. 2021;118:e2016391118. doi: 10.1073/pnas.2016391118. PubMed DOI PMC

Milo R., Phillips R. Bionumbers. [(accessed on 30 October 2022)]. Available online: http://bionumbers.hms.harvard.edu/

Wallden M., Fange D., Lundius E.G., Baltekin Ö., Elf J. The Synchronization of Replication and Division Cycles in Individual E. Coli Cells. Cell. 2016;166:729. doi: 10.1016/j.cell.2016.06.052. PubMed DOI

Kuchel P.W., Chapman B.E., Bubb W.A., Hansen P.E., Durrant C.J., Hertzberg M.P. Magnetic susceptibility: Solutions, emulsions, and cells. Concepts Magn. Reson. Educ. J. 2003;18:56–71. doi: 10.1002/cmr.a.10066. DOI

Biedermann A.R., Pettke T., Koch C.B., Hirt A.M. Magnetic anisotropy in clinopyroxene and orthopyroxene single crystals. Am. Mineral. 1968;53:406–415. doi: 10.1002/2014JB011678. DOI

Liu P.Y., Chin L.K., Ser W., Ayi T.C., Yap P.H., Bourouina T., Leprince-Wang Y. Real-time Measurement of Single Bacterium’s Refractive Index Using Optofluidic Immersion Refractometry. Procedia Eng. 2014;87:356–359. doi: 10.1016/j.proeng.2014.11.743. DOI

Semsey S., Andersson A.M.C., Krishna S., Jensen M.H., Massé E., Sneppen K. Genetic regulation of fluxes: Iron homeostasis of Escherichia coli. Nucleic. Acids. Res. 2006;34:4960–4967. doi: 10.1093/nar/gkl627. PubMed DOI PMC

Fasnacht M., Polacek N. Oxidative Stress in Bacteria and the Central Dogma of Molecular Biology. Front. Mol. Biosci. 2021;8:671037. doi: 10.3389/fmolb.2021.671037. PubMed DOI PMC

Nies D.H. Resistance to cadmium, cobalt, zinc, and nickel in microbes. Plasmid. 1992;27:17–28. doi: 10.1016/0147-619X(92)90003-S. PubMed DOI

Hill P.J., Stritzker J., Scadeng M., Geissinger U., Haddad D., Basse-Lüsebrink T.C., Gbureck U., Jakob P., Szalay A.A. Magnetic resonance imaging of tumors colonized with bacterial ferritin-expressing Escherichia coli. PLoS ONE. 2011;6:e25409. doi: 10.1371/journal.pone.0025409. PubMed DOI PMC

García-Prieto A., Alonso J., Muñoz D., Marcano L., de Cerio A.A.D., Fernández de Luis R., Orue I., Mathon O., Muela A., Fdez-Gubieda M.L. On the Mineral Core of Ferritin-like Proteins: Structural and Magnetic Characterization. Nanoscale. 2016;8:1088. doi: 10.1039/C5NR04446D. PubMed DOI