Wednesday, September 29 |
09:00 - 09:50 |
Helen Byrne: (Byrne + Alarcon, Part I) A multiscale model of complex endothelial cell dynamics in early angiogenesis ↓ We introduce a hybrid two-dimensional multiscale model of angiogenesis, the process by which endothelial cells (ECs) migrate from a pre-existing vascular bed in response to local environmental cues and cell-cell interactions, to create a new vascular network. Recent experimental studies have highlighted the central role of cell rearrangements in the formation of angiogenic networks. Our model accounts for this phenomenon via the heterogeneous response of ECs to their microenvironment. These cell rearrangements, in turn, dynamically remodel the local environment. The model reproduces characteristic features of angiogenic sprouting that include branching, chemotactic sensitivity, the brush border effect, and cell mixing. These properties, rather than being hardwired into the model, emerge naturally from the gene expression patterns of individual cells. After calibrating and validating our model against experimental data, we use it to predict how the structure of the vascular network changes as the baseline gene expression levels of the VEGF-Delta-Notch pathway, and the composition of the extracellular environment, vary. In order to investigate the impact of cell rearrangements on the vascular network structure, we introduce the mixing measure, a scalar metric that quantifies cell mixing as the vascular network grows. We calculate the mixing measure for the simulated vascular networks generated by ECs of different lineages (wild-type cells and mutant cells with impaired expression of a specific receptor). Our results show that the time evolution of the mixing measure is directly correlated to the generic features of the vascular branching pattern, thus, supporting the hypothesis that cell rearrangements play an essential role in sprouting angiogenesis. Furthermore, we predict that lower cell rearrangement leads to an imbalance between branching and sprout elongation. Since the computation of this statistic requires only individual cell trajectories, it can be computed for networks generated in biological experiments, making it a potential biomarker for pathological angiogenesis. (Zoom) |
10:00 - 10:50 |
Tomás Alarcón: (Byrne + Alarcon, Part II) A multiscale model of complex endothelial cell dynamics in early angiogenesis ↓ We introduce a hybrid two-dimensional multiscale model of angiogenesis, the process by which endothelial cells (ECs) migrate from a pre-existing vascular bed in response to local environmental cues and cell-cell interactions, to create a new vascular network. Recent experimental studies have highlighted the central role of cell rearrangements in the formation of angiogenic networks. Our model accounts for this phenomenon via the heterogeneous response of ECs to their microenvironment. These cell rearrangements, in turn, dynamically remodel the local environment. The model reproduces characteristic features of angiogenic sprouting that include branching, chemotactic sensitivity, the brush border effect, and cell mixing. These properties, rather than being hardwired into the model, emerge naturally from the gene expression patterns of individual cells. After calibrating and validating our model against experimental data, we use it to predict how the structure of the vascular network changes as the baseline gene expression levels of the VEGF-Delta-Notch pathway, and the composition of the extracellular environment, vary. In order to investigate the impact of cell rearrangements on the vascular network structure, we introduce the mixing measure, a scalar metric that quantifies cell mixing as the vascular network grows. We calculate the mixing measure for the simulated vascular networks generated by ECs of different lineages (wild-type cells and mutant cells with impaired expression of a specific receptor). Our results show that the time evolution of the mixing measure is directly correlated to the generic features of the vascular branching pattern, thus, supporting the hypothesis that cell rearrangements play an essential role in sprouting angiogenesis. Furthermore, we predict that lower cell rearrangement leads to an imbalance between branching and sprout elongation. Since the computation of this statistic requires only individual cell trajectories, it can be computed for networks generated in biological experiments, making it a potential biomarker for pathological angiogenesis. (Zoom) |
11:00 - 11:50 |
Brian Camley: Contact inhibition of locomotion and geometry ↓ For cells to cooperate in healing a wound or work together to follow a signal, they must coordinate their motion. One stereotyped behavior found in many cell types is "contact inhibition of locomotion" (CIL), in which cells that collide with one another repolarize away from contact. Experiments studying CIL are often performed on flat rigid two-dimensional substrates, unlike the natural fibrous environment of many cells in vivo. How does extracellular matrix geometry and adhesivity affect CIL? First, I will talk about recent experiments by our collaborators in the Nain group, which show that when cells are attached to single suspended nanofibers, the outcomes of CIL can be radically different, with cells walking past each other. Our modeling shows that this likely arises from the additional degrees of freedom that cells have to rotate around the fiber, and can be abolished by forcing cells to attach to two fibers. I will also discuss more recent modeling on how cell-cell collisions can be moderated by the geometry of the cell-substrate contact angle. (Zoom) |
13:00 - 13:50 |
Denise Montell: Orthogonal physical and chemical cues steer migrating Drosophila border cells ↓ Border cell migration in the Drosophila ovary is a relatively simple model for the study of collective, cooperative, cell-on cell migration in vivo that is amenable to live imaging, genetic and optogenetic approaches. Decades of work have revealed the secreted signals that govern which 6 of the 850 epithelial cells acquire the ability to migrate, when during development they do so, and where they go. In addition to biochemical signals, moving cells also sense and respond to physical features of the microenvironment; however, the significance of tissue topography was unknown. We used Drosophila border cells to study how chemical and physical information influences path selection. Although chemical cues were thought to be sufficient, live imaging, genetics, modeling, and simulations show that microtopography is also important. Chemoattractants promote predominantly posterior movement, whereas tissue architecture presents orthogonal information, a path of least resistance concentrated near the center of the egg chamber. E-cadherin supplies a permissive haptotactic cue. Our results provide insight into how cells integrate and prioritize topographical, adhesive, and chemoattractant cues to choose one path among many. New findings on the role of septin proteins in border cell morphology and migration will also be presented. (Zoom) |
14:00 - 14:50 |
Kevin Painter: Models for the collective navigation: from cells to whales ↓ In collective navigation, a population travels as a group from an origin to a destination. Famous examples include the migrations of birds, between their winter and summer grounds, but collective movements also extend down to microorganisms and cell populations. Collective navigation is believed to improve the efficiency of migration, for example through the presence of more knowledgeable individuals that guide naive members ("leader-follower behaviour") or through the averaging out of individual undertainty ("many wrongs"). In this talk I will describe individual and continuous approaches for modelling collective navigation. The individual based model is predicated on a random walk model, where individuals supplement their own inherent guidance information with information acquired from other group members. The continuous model is based on a nonlocal hyperbolic PDE system. We investigate the point at which group information becomes beneficial to migration and how it can help a population navigate through "information voids", i.e. areas with negligible guidance information. We also explore the effectiveness of different modes through which a leader can herd a group of naïve followers. (Zoom) |
15:00 - 16:30 |
Thomas Hillen: Free discussion in gathertown (Gathertown) |