Modelling phagosomal lipid networks that regulate actin assembly
- Autores
- Kühnel, Marck; Mayorga, Luis Segundo; Dandekar, Thomas; Thakar, Juilee; Schwarz, Roland; Anes, Elsa; Griffiths, Gareth; Reich, Jens
- Año de publicación
- 2008
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Background: When purified phagosomes are incubated in the presence of actin under appropriate conditions, microfilaments start growing from the membrane in a process that is affected by ATP and the lipid composition of the membrane. Isolated phagosomes are metabolically active organelles that contain enzymes and metabolites necessary for lipid interconversion. Hence, addition of ATP, lipids, and actin to the system alter the steady-state composition of the phagosomal membrane at the same time that the actin nucleation is initiated. Our aim was to model all these processes in parallel. Results: We compiled detailed experimental data on the effects of different lipids and ATP on actin nucleation and we investigated experimentally lipid interconversion and ATP metabolism in phagosomes by using suitable radioactive compounds. In a first step, a complex lipid network interconnected by chemical reactions catalyzed by known enzymes was modelled in COPASI (Complex Pathway Simulator). However, several lines of experimental evidence indicated that only the phosphatidylinositol branch of the network was active, an observation that dramatically reduced the number of parameters in the model. The results also indicated that a lipid network-independent ATP-consuming activity should be included in the model. When this activity was introduced, the set of differential equations satisfactorily reproduced the experimental data. On the other hand, a molecular mechanism connecting membrane lipids, ATP, and the actin nucleation process is still missing. We therefore adopted a phenomenological (black-box) approach to represent the empirical observations. We proposed that lipids and ATP influence the dynamic interconversion between active and inactive actin nucleation sites. With this simple model, all the experimental data were satisfactorily fitted with a single positive parameter per lipid and ATP. Conclusion: By establishing an active 'dialogue' between an initial complex model and experimental observations, we could narrow the set of differential equations and parameters required to characterize the time-dependent changes of metabolites influencing actin nucleation on phagosomes. For this, the global model was dissected into three sub-models: ATP consumption, lipid interconversion, and nucleation of actin on phagosomal membranes. This scheme allowed us to describe this complex system with a relatively small set of differential equations and kinetic parameters that satisfactorily reproduced the experimental data.
Fil: Kühnel, Marck. European Molecular Biology Laboratory; Alemania
Fil: Mayorga, Luis Segundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. European Molecular Biology Laboratory; Alemania
Fil: Dandekar, Thomas. Universität Würzburg; Alemania
Fil: Thakar, Juilee. State University of Pennsylvania; Estados Unidos
Fil: Schwarz, Roland. Universität Würzburg; Alemania
Fil: Anes, Elsa. Universidad de Lisboa; Portugal
Fil: Griffiths, Gareth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. European Molecular Biology Laboratory; Alemania
Fil: Reich, Jens. Max-Delbrück-Centrum für Molekulare Medizin; Alemania - Materia
-
MATHEMATICAL MODEL
PHAGOSOME
MEMBRANE LIPIDS
PHOSPHOLIPIDS - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/127528
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Modelling phagosomal lipid networks that regulate actin assemblyKühnel, MarckMayorga, Luis SegundoDandekar, ThomasThakar, JuileeSchwarz, RolandAnes, ElsaGriffiths, GarethReich, JensMATHEMATICAL MODELPHAGOSOMEMEMBRANE LIPIDSPHOSPHOLIPIDShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Background: When purified phagosomes are incubated in the presence of actin under appropriate conditions, microfilaments start growing from the membrane in a process that is affected by ATP and the lipid composition of the membrane. Isolated phagosomes are metabolically active organelles that contain enzymes and metabolites necessary for lipid interconversion. Hence, addition of ATP, lipids, and actin to the system alter the steady-state composition of the phagosomal membrane at the same time that the actin nucleation is initiated. Our aim was to model all these processes in parallel. Results: We compiled detailed experimental data on the effects of different lipids and ATP on actin nucleation and we investigated experimentally lipid interconversion and ATP metabolism in phagosomes by using suitable radioactive compounds. In a first step, a complex lipid network interconnected by chemical reactions catalyzed by known enzymes was modelled in COPASI (Complex Pathway Simulator). However, several lines of experimental evidence indicated that only the phosphatidylinositol branch of the network was active, an observation that dramatically reduced the number of parameters in the model. The results also indicated that a lipid network-independent ATP-consuming activity should be included in the model. When this activity was introduced, the set of differential equations satisfactorily reproduced the experimental data. On the other hand, a molecular mechanism connecting membrane lipids, ATP, and the actin nucleation process is still missing. We therefore adopted a phenomenological (black-box) approach to represent the empirical observations. We proposed that lipids and ATP influence the dynamic interconversion between active and inactive actin nucleation sites. With this simple model, all the experimental data were satisfactorily fitted with a single positive parameter per lipid and ATP. Conclusion: By establishing an active 'dialogue' between an initial complex model and experimental observations, we could narrow the set of differential equations and parameters required to characterize the time-dependent changes of metabolites influencing actin nucleation on phagosomes. For this, the global model was dissected into three sub-models: ATP consumption, lipid interconversion, and nucleation of actin on phagosomal membranes. This scheme allowed us to describe this complex system with a relatively small set of differential equations and kinetic parameters that satisfactorily reproduced the experimental data.Fil: Kühnel, Marck. European Molecular Biology Laboratory; AlemaniaFil: Mayorga, Luis Segundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. European Molecular Biology Laboratory; AlemaniaFil: Dandekar, Thomas. Universität Würzburg; AlemaniaFil: Thakar, Juilee. State University of Pennsylvania; Estados UnidosFil: Schwarz, Roland. Universität Würzburg; AlemaniaFil: Anes, Elsa. Universidad de Lisboa; PortugalFil: Griffiths, Gareth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. European Molecular Biology Laboratory; AlemaniaFil: Reich, Jens. Max-Delbrück-Centrum für Molekulare Medizin; AlemaniaBioMed Central2008-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/127528Kühnel, Marck; Mayorga, Luis Segundo; Dandekar, Thomas; Thakar, Juilee; Schwarz, Roland; et al.; Modelling phagosomal lipid networks that regulate actin assembly; BioMed Central; Bmc Systems Biology; 2; 12-2008; 107-1081752-0509CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://bmcsystbiol.biomedcentral.com/articles/10.1186/1752-0509-2-107info:eu-repo/semantics/altIdentifier/doi/10.1186/1752-0509-2-107info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:30:12Zoai:ri.conicet.gov.ar:11336/127528instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:30:12.69CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Modelling phagosomal lipid networks that regulate actin assembly |
title |
Modelling phagosomal lipid networks that regulate actin assembly |
spellingShingle |
Modelling phagosomal lipid networks that regulate actin assembly Kühnel, Marck MATHEMATICAL MODEL PHAGOSOME MEMBRANE LIPIDS PHOSPHOLIPIDS |
title_short |
Modelling phagosomal lipid networks that regulate actin assembly |
title_full |
Modelling phagosomal lipid networks that regulate actin assembly |
title_fullStr |
Modelling phagosomal lipid networks that regulate actin assembly |
title_full_unstemmed |
Modelling phagosomal lipid networks that regulate actin assembly |
title_sort |
Modelling phagosomal lipid networks that regulate actin assembly |
dc.creator.none.fl_str_mv |
Kühnel, Marck Mayorga, Luis Segundo Dandekar, Thomas Thakar, Juilee Schwarz, Roland Anes, Elsa Griffiths, Gareth Reich, Jens |
author |
Kühnel, Marck |
author_facet |
Kühnel, Marck Mayorga, Luis Segundo Dandekar, Thomas Thakar, Juilee Schwarz, Roland Anes, Elsa Griffiths, Gareth Reich, Jens |
author_role |
author |
author2 |
Mayorga, Luis Segundo Dandekar, Thomas Thakar, Juilee Schwarz, Roland Anes, Elsa Griffiths, Gareth Reich, Jens |
author2_role |
author author author author author author author |
dc.subject.none.fl_str_mv |
MATHEMATICAL MODEL PHAGOSOME MEMBRANE LIPIDS PHOSPHOLIPIDS |
topic |
MATHEMATICAL MODEL PHAGOSOME MEMBRANE LIPIDS PHOSPHOLIPIDS |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Background: When purified phagosomes are incubated in the presence of actin under appropriate conditions, microfilaments start growing from the membrane in a process that is affected by ATP and the lipid composition of the membrane. Isolated phagosomes are metabolically active organelles that contain enzymes and metabolites necessary for lipid interconversion. Hence, addition of ATP, lipids, and actin to the system alter the steady-state composition of the phagosomal membrane at the same time that the actin nucleation is initiated. Our aim was to model all these processes in parallel. Results: We compiled detailed experimental data on the effects of different lipids and ATP on actin nucleation and we investigated experimentally lipid interconversion and ATP metabolism in phagosomes by using suitable radioactive compounds. In a first step, a complex lipid network interconnected by chemical reactions catalyzed by known enzymes was modelled in COPASI (Complex Pathway Simulator). However, several lines of experimental evidence indicated that only the phosphatidylinositol branch of the network was active, an observation that dramatically reduced the number of parameters in the model. The results also indicated that a lipid network-independent ATP-consuming activity should be included in the model. When this activity was introduced, the set of differential equations satisfactorily reproduced the experimental data. On the other hand, a molecular mechanism connecting membrane lipids, ATP, and the actin nucleation process is still missing. We therefore adopted a phenomenological (black-box) approach to represent the empirical observations. We proposed that lipids and ATP influence the dynamic interconversion between active and inactive actin nucleation sites. With this simple model, all the experimental data were satisfactorily fitted with a single positive parameter per lipid and ATP. Conclusion: By establishing an active 'dialogue' between an initial complex model and experimental observations, we could narrow the set of differential equations and parameters required to characterize the time-dependent changes of metabolites influencing actin nucleation on phagosomes. For this, the global model was dissected into three sub-models: ATP consumption, lipid interconversion, and nucleation of actin on phagosomal membranes. This scheme allowed us to describe this complex system with a relatively small set of differential equations and kinetic parameters that satisfactorily reproduced the experimental data. Fil: Kühnel, Marck. European Molecular Biology Laboratory; Alemania Fil: Mayorga, Luis Segundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. European Molecular Biology Laboratory; Alemania Fil: Dandekar, Thomas. Universität Würzburg; Alemania Fil: Thakar, Juilee. State University of Pennsylvania; Estados Unidos Fil: Schwarz, Roland. Universität Würzburg; Alemania Fil: Anes, Elsa. Universidad de Lisboa; Portugal Fil: Griffiths, Gareth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. European Molecular Biology Laboratory; Alemania Fil: Reich, Jens. Max-Delbrück-Centrum für Molekulare Medizin; Alemania |
description |
Background: When purified phagosomes are incubated in the presence of actin under appropriate conditions, microfilaments start growing from the membrane in a process that is affected by ATP and the lipid composition of the membrane. Isolated phagosomes are metabolically active organelles that contain enzymes and metabolites necessary for lipid interconversion. Hence, addition of ATP, lipids, and actin to the system alter the steady-state composition of the phagosomal membrane at the same time that the actin nucleation is initiated. Our aim was to model all these processes in parallel. Results: We compiled detailed experimental data on the effects of different lipids and ATP on actin nucleation and we investigated experimentally lipid interconversion and ATP metabolism in phagosomes by using suitable radioactive compounds. In a first step, a complex lipid network interconnected by chemical reactions catalyzed by known enzymes was modelled in COPASI (Complex Pathway Simulator). However, several lines of experimental evidence indicated that only the phosphatidylinositol branch of the network was active, an observation that dramatically reduced the number of parameters in the model. The results also indicated that a lipid network-independent ATP-consuming activity should be included in the model. When this activity was introduced, the set of differential equations satisfactorily reproduced the experimental data. On the other hand, a molecular mechanism connecting membrane lipids, ATP, and the actin nucleation process is still missing. We therefore adopted a phenomenological (black-box) approach to represent the empirical observations. We proposed that lipids and ATP influence the dynamic interconversion between active and inactive actin nucleation sites. With this simple model, all the experimental data were satisfactorily fitted with a single positive parameter per lipid and ATP. Conclusion: By establishing an active 'dialogue' between an initial complex model and experimental observations, we could narrow the set of differential equations and parameters required to characterize the time-dependent changes of metabolites influencing actin nucleation on phagosomes. For this, the global model was dissected into three sub-models: ATP consumption, lipid interconversion, and nucleation of actin on phagosomal membranes. This scheme allowed us to describe this complex system with a relatively small set of differential equations and kinetic parameters that satisfactorily reproduced the experimental data. |
publishDate |
2008 |
dc.date.none.fl_str_mv |
2008-12 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/127528 Kühnel, Marck; Mayorga, Luis Segundo; Dandekar, Thomas; Thakar, Juilee; Schwarz, Roland; et al.; Modelling phagosomal lipid networks that regulate actin assembly; BioMed Central; Bmc Systems Biology; 2; 12-2008; 107-108 1752-0509 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/127528 |
identifier_str_mv |
Kühnel, Marck; Mayorga, Luis Segundo; Dandekar, Thomas; Thakar, Juilee; Schwarz, Roland; et al.; Modelling phagosomal lipid networks that regulate actin assembly; BioMed Central; Bmc Systems Biology; 2; 12-2008; 107-108 1752-0509 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://bmcsystbiol.biomedcentral.com/articles/10.1186/1752-0509-2-107 info:eu-repo/semantics/altIdentifier/doi/10.1186/1752-0509-2-107 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
BioMed Central |
publisher.none.fl_str_mv |
BioMed Central |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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13.070432 |