András Szabó

CV (pdf), Google Scholar profile, OrchID: 0000-0002-8924-038X

research

Collective cell migration

Collective cell migration of the neural crest UCL

D The neural crest is a transient cell population that migrates large distances collectively during development to contribute to most of the organs in the vertebrate body. The neural crest undergo EMT and acquire the cellular property of contact inhibition of locomotion (CIL). CIL is facilitated by a switch of E- to N-cadherin which allows the cells to repolarize and tear away from each other. During their migration, the neural crest is confined into streams by several extacellular molecules including the proteoglycan Versican, they undergo autocrine(C3a) and paracrine (Sdf1) chemotaxis, and perform CIL with each other and the neighbouring placodal cells that secrete Sdf1.


Endothelial monolayers exhibit streaming behaviour in vitro ELTE

Endothelial cells keep their motility in vitro even for some time after growing into a confluent monolayer. Streams of several cell-widths form and disappear spontaneously, often creating cellular vortices and shear lines. We have characterised their streaming motion with a novel 2-dimensional velocity correlation function and gave a possible explanation to their behaviour. For this end, we introduced polarised cells to the cellular Potts model framework and gave a systematic analysis of the new model. The model readily describes the observations quantitatively.


Morphogenesis in development

Epiboly through radial intercalation driven by short-range chemotaxis UCL

Epiboly is the large-scale morphogenetic process whereby a thick layer of tissue spreads and concomitantly thins in the perpendicular direction. During early development of the frog one hemisphere undergoes epiboly to cover the whole embryo. One of the essential drivers of this process is the radial intercalation of the inner cells towards the superficial cells that secrete a chemoattractant.


Heart development and endothelial cell movement in the forming aorta KUMC-ELTE

Under normal cicrumstances, endothelial cells in the forming aorta perform a spiraling motion towards the forming heart, before the onset of the circulation. With the aid of time-lapse fluorescent microscopy this motion is resolved in 3-dimensions. Cell-autonomous motility is devised from the observed cellular and extracellular matrix (fibrillin) motion.

The forming heart of quail embryos is investigated with time-lapse fluorescent microscopy. Stages of development are introduced, and individual cell and tissue motion is analysed. The 3-dimensional velocity-field of the tracked parts is reconstructed, eventually yielding an overall picture of tissue and active cell motion within the heart region. A spiralling motion towards the heart is observable at the inflow tubes, very similar to the one apparent at the aortae.


Network formation of tissue cells

Preferential attachment to elongated cells ELTE

Several types of tissue cells are capable of forming networks similar to the primary vascular plexus, the predecessor of the vascular network in embryos. We have found that the cells move from seemingly random positions to connect into a network, even under circumstances that prevent the previously suggested mechanisms, such as chemotaxis. A possible mechanism for this phenomenon is the preferential attachment to elongated cells. Although the molecular mechanism behind the hypothesis remains unclear, computer simulations reveal that cellular networks can emerge. The hypothesis was implemented in the cellular Potts model as well as a simple model, where cells are represented by interacting points.


Vascular sprouting ELTE

An important mechanism in remodeling existing networks is the formation of new sprouts from estabilished branches. Sprouts are initiated and pulled by tip cells, a specialized, actively moving sub-population. We argue, that the remainder, bulk of the population must also perform active motion, otherwise the sprouts would break up in the same fashion as water flowing from the tap breaks up into droplets. The assumption is supported by modeling. We used the cellular Potts model framework, with or without cells preferentially attached to elongated neighbours and a tip-cell with persistent active motility. The model is able to reproduce sprout initiation and growth. Cells without preferential attachment are unable to sustain the continuous growth of the sprout and thus the brach breaks, whereas if cells take an active part in the process, sprout growth is supported for an extended time and length.


Computational tumor biology

Evolutionary tumor growth modelling NCSB-CWI

Tumor behavior on a longer time scale is defined by the mutation and uncontrolled proliferation of malfunctioning cells. Several hypotheses exists on the actual time course and driving mechanisms of the development of such an aggregate. In the classical view (Nowell, 1976) the population goes through a well defined sequence of stages acquiring new phenotypes by gathering mutations of genes in a fixed sequence. More recent technology and research results enables us to look at the process in more detail, in terms of various phenotypes and their competition. Cell-based multi-level computational modelling is an especially useful tool in uncovering the dynamics and mechanisms underlying such complex systems.


Simulation of active tumor invasion ELTE

Active cell motion plays an important role in tumor invasion. By leaving the initial aggregate, cells are able to colonize new areas and thus spread the malignancy to larger areas. To understand the effect of a spatially organized microenvironment, we model active cell motion in ordered filaments of extracellular matrix. We show, that such an environment enhances persistent migration and therefore contributes to the dynamics. Furthermore, persistence in the cells' motion is also necessary to correctly describe invasion speed.


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