A 3D multi-agent-based model for lumen morphogenesis: the role of the biophysical properties of the extracellular matrix

Camacho-Gómez, Daniel (Universidad de Zaragoza) ; García-Aznar, José Manuel (Universidad de Zaragoza) ; Gómez-Benito, María José (Universidad de Zaragoza)

Resumen: The correct function of many organs depends on proper lumen morphogenesis, which requires the orchestration of both biological and mechanical aspects. However, how these factors coordinate is not yet fully understood. Here, we focus on the development of a mechanistic model for computationally simulating lumen morphogenesis. In particular, we consider the hydrostatic pressure generated by the cells'' fluid secretion as the driving force and the density of the extracellular matrix as regulators of the process. For this purpose, we develop a 3D agent-based-model for lumen morphogenesis that includes cells'' fluid secretion and the density of the extracellular matrix. Moreover, this computer-based model considers the variation in the biological behavior of cells in response to the mechanical forces that they sense. Then, we study the formation of the lumen under different-mechanical scenarios and conclude that an increase in the matrix density reduces the lumen volume and hinders lumen morphogenesis. Finally, we show that the model successfully predicts normal lumen morphogenesis when the matrix density is physiological and aberrant multilumen formation when the matrix density is excessive.

Idioma: Inglés

DOI: 10.1007/s00366-022-01654-1

Año: 2022

Publicado en: ENGINEERING WITH COMPUTERS 34 (2022), 4135–4149
ISSN: 0177-0667

Factor impacto JCR: 8.7 (2022)

Categ. JCR: ENGINEERING, MECHANICAL rank: 4 / 136 = 0.029 (2022) - Q1 - T1
Categ. JCR: COMPUTER SCIENCE, INTERDISCIPLINARY APPLICATIONS rank: 12 / 110 = 0.109 (2022) - Q1 - T1

Factor impacto CITESCORE: 13.4 - Engineering (Q1) - Mathematics (Q1) - Computer Science (Q1)

Factor impacto SCIMAGO: 1.096 - Computer Science Applications (Q1) - Software (Q1) - Modeling and Simulation (Q1) - Engineering (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/EC/H2020/826494/EU/PRedictive In-silico Multiscale Analytics to support cancer personalized diaGnosis and prognosis, Empowered by imaging biomarkers/PRIMAGE
Financiación: info:eu-repo/grantAgreement/ES/MICINN/RTI2018-094494-B-C21

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Mec.Med.Cont. y Teor.Est. (Dpto. Ingeniería Mecánica)