Dynamics of chromosome organization in a minimal bacterial cell
Computational models of cells cannot be considered complete unless they include the most fundamental process of life, the replication and inheritance of genetic material. By creating a computational framework to model systems of replicating bacterial chromosomes as polymers at 10 bp resolution with...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1214962/full |
| _version_ | 1797748950094053376 |
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| author | Benjamin R. Gilbert Zane R. Thornburg Troy A. Brier Jan A. Stevens Fabian Grünewald John E. Stone John E. Stone Siewert J. Marrink Zaida Luthey-Schulten Zaida Luthey-Schulten Zaida Luthey-Schulten |
| author_facet | Benjamin R. Gilbert Zane R. Thornburg Troy A. Brier Jan A. Stevens Fabian Grünewald John E. Stone John E. Stone Siewert J. Marrink Zaida Luthey-Schulten Zaida Luthey-Schulten Zaida Luthey-Schulten |
| author_sort | Benjamin R. Gilbert |
| collection | DOAJ |
| description | Computational models of cells cannot be considered complete unless they include the most fundamental process of life, the replication and inheritance of genetic material. By creating a computational framework to model systems of replicating bacterial chromosomes as polymers at 10 bp resolution with Brownian dynamics, we investigate changes in chromosome organization during replication and extend the applicability of an existing whole-cell model (WCM) for a genetically minimal bacterium, JCVI-syn3A, to the entire cell-cycle. To achieve cell-scale chromosome structures that are realistic, we model the chromosome as a self-avoiding homopolymer with bending and torsional stiffnesses that capture the essential mechanical properties of dsDNA in Syn3A. In addition, the conformations of the circular DNA must avoid overlapping with ribosomes identitied in cryo-electron tomograms. While Syn3A lacks the complex regulatory systems known to orchestrate chromosome segregation in other bacteria, its minimized genome retains essential loop-extruding structural maintenance of chromosomes (SMC) protein complexes (SMC-scpAB) and topoisomerases. Through implementing the effects of these proteins in our simulations of replicating chromosomes, we find that they alone are sufficient for simultaneous chromosome segregation across all generations within nested theta structures. This supports previous studies suggesting loop-extrusion serves as a near-universal mechanism for chromosome organization within bacterial and eukaryotic cells. Furthermore, we analyze ribosome diffusion under the influence of the chromosome and calculate in silico chromosome contact maps that capture inter-daughter interactions. Finally, we present a methodology to map the polymer model of the chromosome to a Martini coarse-grained representation to prepare molecular dynamics models of entire Syn3A cells, which serves as an ultimate means of validation for cell states predicted by the WCM. |
| first_indexed | 2024-03-12T16:12:19Z |
| format | Article |
| id | doaj.art-42b2539a78d14ebabeca3d47e234ce28 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-03-12T16:12:19Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-42b2539a78d14ebabeca3d47e234ce282023-08-09T12:08:30ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-08-011110.3389/fcell.2023.12149621214962Dynamics of chromosome organization in a minimal bacterial cellBenjamin R. Gilbert0Zane R. Thornburg1Troy A. Brier2Jan A. Stevens3Fabian Grünewald4John E. Stone5John E. Stone6Siewert J. Marrink7Zaida Luthey-Schulten8Zaida Luthey-Schulten9Zaida Luthey-Schulten10Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, United StatesDepartment of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, United StatesDepartment of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, United StatesMolecular Dynamics Group, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, NetherlandsMolecular Dynamics Group, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, NetherlandsNVIDIA Corporation, Santa Clara, CA, United StatesNIH Center for Macromolecular Modeling and Bioinformatics, Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL, United StatesMolecular Dynamics Group, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, NetherlandsDepartment of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, United StatesNIH Center for Macromolecular Modeling and Bioinformatics, Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL, United StatesNSF Center for the Physics of Living Cells, Department of Physics, University of Illinois at Urbana-Champaign, Urbana, IL, United StatesComputational models of cells cannot be considered complete unless they include the most fundamental process of life, the replication and inheritance of genetic material. By creating a computational framework to model systems of replicating bacterial chromosomes as polymers at 10 bp resolution with Brownian dynamics, we investigate changes in chromosome organization during replication and extend the applicability of an existing whole-cell model (WCM) for a genetically minimal bacterium, JCVI-syn3A, to the entire cell-cycle. To achieve cell-scale chromosome structures that are realistic, we model the chromosome as a self-avoiding homopolymer with bending and torsional stiffnesses that capture the essential mechanical properties of dsDNA in Syn3A. In addition, the conformations of the circular DNA must avoid overlapping with ribosomes identitied in cryo-electron tomograms. While Syn3A lacks the complex regulatory systems known to orchestrate chromosome segregation in other bacteria, its minimized genome retains essential loop-extruding structural maintenance of chromosomes (SMC) protein complexes (SMC-scpAB) and topoisomerases. Through implementing the effects of these proteins in our simulations of replicating chromosomes, we find that they alone are sufficient for simultaneous chromosome segregation across all generations within nested theta structures. This supports previous studies suggesting loop-extrusion serves as a near-universal mechanism for chromosome organization within bacterial and eukaryotic cells. Furthermore, we analyze ribosome diffusion under the influence of the chromosome and calculate in silico chromosome contact maps that capture inter-daughter interactions. Finally, we present a methodology to map the polymer model of the chromosome to a Martini coarse-grained representation to prepare molecular dynamics models of entire Syn3A cells, which serves as an ultimate means of validation for cell states predicted by the WCM.https://www.frontiersin.org/articles/10.3389/fcell.2023.1214962/fullwhole-cell modelingchromosome replicationchromosome segregationbrownian dynamicssmc proteinstopoisomerase |
| spellingShingle | Benjamin R. Gilbert Zane R. Thornburg Troy A. Brier Jan A. Stevens Fabian Grünewald John E. Stone John E. Stone Siewert J. Marrink Zaida Luthey-Schulten Zaida Luthey-Schulten Zaida Luthey-Schulten Dynamics of chromosome organization in a minimal bacterial cell Frontiers in Cell and Developmental Biology whole-cell modeling chromosome replication chromosome segregation brownian dynamics smc proteins topoisomerase |
| title | Dynamics of chromosome organization in a minimal bacterial cell |
| title_full | Dynamics of chromosome organization in a minimal bacterial cell |
| title_fullStr | Dynamics of chromosome organization in a minimal bacterial cell |
| title_full_unstemmed | Dynamics of chromosome organization in a minimal bacterial cell |
| title_short | Dynamics of chromosome organization in a minimal bacterial cell |
| title_sort | dynamics of chromosome organization in a minimal bacterial cell |
| topic | whole-cell modeling chromosome replication chromosome segregation brownian dynamics smc proteins topoisomerase |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1214962/full |
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