title: Quantification of topological features in cell meshes to explore E-cadherin dysfunction.
abstract: In cancer, defective E-cadherin leads to cell detachment, migration and metastization. Further, alterations mediated by E-cadherin dysfunction affect cell topology and tissue organization. Herein, we propose a novel quantitative approach, based on microscopy images, to analyse abnormal cellular distribution patterns. We generated undirected graphs composed by sets of triangles which accurately reproduce cell positioning and structural organization within each image. Network analysis was developed by exploring triangle geometric features, namely area, edges length and formed angles, as well as their variance, when compared with the respective equilateral triangles. We generated synthetic networks, mimicking the diversity of cell-cell interaction patterns, and evaluated the applicability of the selected metrics to study topological features. Cells expressing wild-type E-cadherin and cancer-related mutants were used to validate our strategy. Specifically, A634V, R749W and P799R cancer-causing mutants present more disorganized spatial distribution when compared with wild-type cells. Moreover, P799R exhibited higher length and angle distortions and abnormal cytoskeletal organization, suggesting the formation of very dynamic and plastic cellular interactions. Hence, topological analysis of cell network diagrams is an effective tool to quantify changes in cell-cell interactions and, importantly, it can be applied to a myriad of processes, namely tissue morphogenesis and cancer.
authors.affiliation: Institute for Systems and Robotics, Instituto Superior Técnico, Lisboa, Portugal.
authors.forename: Tânia
authors.initials: T
authors.lastname: Mestre
authors.affiliation: Instituto de Investigação e Inovação em Saúde (i3S), Porto, Portugal.|Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Figueiredo
authors.affiliation: Instituto de Investigação e Inovação em Saúde (i3S), Porto, Portugal.|Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal.
authors.forename: Ana Sofia
authors.initials: AS
authors.lastname: Ribeiro
authors.affiliation: Instituto de Investigação e Inovação em Saúde (i3S), Porto, Portugal.|Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal.|Department of Pathology and Oncology, Medical Faculty of the University of Porto, Porto, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Paredes
authors.affiliation: Instituto de Investigação e Inovação em Saúde (i3S), Porto, Portugal.|Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal.|Department of Pathology and Oncology, Medical Faculty of the University of Porto, Porto, Portugal.
authors.forename: Raquel
authors.initials: R
authors.lastname: Seruca
authors.affiliation: Institute for Systems and Robotics, Instituto Superior Técnico, Lisboa, Portugal.
authors.forename: João Miguel
authors.initials: JM
authors.lastname: Sanches
mesh_terms: D000818:Animals; D016466:CHO Cells; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002450:Cell Communication; D003412:Cricetulus; D003584:Cytological Techniques / Q000379:methods*; D006801:Humans; D008853:Microscopy / Q000379:methods*; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000473:pathology*
chemical_list: D015820:Cadherins; D050505:Mutant Proteins