Abstract: Recently, the concept of digital twins has gained increasing attention in biology, biomedicine, and healthcare communities. This talk will explore the construction of multiscale models and digital twins as they relate to studying embryo development and blood clot contraction. Robust organ formation in embryos depends on the coordinated regulation of cellular mechanics, yet how mechanobiological processes such as controlled cell-cell and cell-extracellular matrix (ECM) adhesion, actomyosin contractility, membrane stiffness, and internal pressure interlink to generate an organ’s architecture remains poorly understood. In this talk, through iterations between experiments and multiscale model simulations, we will show that the local curvature, height, and nuclear positioning of cells in the Drosophila wing imaginal disc are defined by the concurrent patterning of actomyosin contractility, cell-ECM adhesion, ECM stiffness, and interfacial membrane tension [1,2]. Development and application of surrogate AI models in the context of Digital Twins for sensitivity analysis will be also discussed. The predictions made by the model simulations agree with the experimentally observed changes in shapes and tissue structure during wing disc development. Our findings reflect similar mechanisms of morphogenesis in other developmental contexts as well as potential causes of birth defects.
While blood clot formation has been relatively well studied, little is known about the mechanisms underlying the subsequent structural and mechanical clot remodeling called contraction. Impairment of the clot contraction process is associated with both life-threatening bleeding and thrombotic conditions, such as ischemic stroke, venous thromboembolism, and others. A three-dimensional multiscale model will be described and applied to quantify biomechanical mechanisms of the kinetics of clot deformation, stretching and contraction driven by platelet filopodia-fibrin fiber pulling interactions [3,4]. These results provided novel biological insights since filopodia had been thought of previously as performing mostly a sensory function. The biomechanical mechanisms and modeling approach to be described can potentially apply to studying other blood clotting processes as well as to other systems in which cells are embedded in a filamentous network and exert forces on the extracellular matrix modulated by the substrate stiffness.
Bio: Professor Mark Alber earned his Ph.D. in mathematics at the University of Pennsylvania. He held several positions at the University of Notre Dame including most recently Vincent J. Duncan Family Chair in Applied Mathematics. He is currently Distinguished Professor in the Department of Mathematics and Director of the Interdisciplinary Center for Data-Driven Modeling in Biology, University of California, Riverside. Dr. Alber was elected in 2011 Fellow of the American Association for the Advancement of Science (AAAS) and received 2024 US Fulbright Scholar Award (The Netherlands). He is currently a section editor in systems biology of PLoS Computational Biology and member of editorial boards of Bulletin of Mathematical Biology and Journal of the Royal Society Interface.
Abstract: Recently, the concept of digital twins has gained increasing attention in biology, biomedicine, and healthcare communities. This talk will explore the construction of multiscale models and digital twins as they relate to studying embryo development and blood clot contraction. Robust organ formation in embryos depends on the coordinated regulation of cellular mechanics, yet how mechanobiological processes such as controlled cell-cell and cell-extracellular matrix (ECM) adhesion, actomyosin contractility, membrane stiffness, and internal pressure interlink to generate an organ’s architecture remains poorly understood. In this talk, through iterations between experiments and multiscale model simulations, we will show that the local curvature, height, and nuclear positioning of cells in the Drosophila wing imaginal disc are defined by the concurrent patterning of actomyosin contractility, cell-ECM adhesion, ECM stiffness, and interfacial membrane tension [1,2]. Development and application of surrogate AI models in the context of Digital Twins for sensitivity analysis will be also discussed. The predictions made by the model simulations agree with the experimentally observed changes in shapes and tissue structure during wing disc development. Our findings reflect similar mechanisms of morphogenesis in other developmental contexts as well as potential causes of birth defects.
While blood clot formation has been relatively well studied, little is known about the mechanisms underlying the subsequent structural and mechanical clot remodeling called contraction. Impairment of the clot contraction process is associated with both life-threatening bleeding and thrombotic conditions, such as ischemic stroke, venous thromboembolism, and others. A three-dimensional multiscale model will be described and applied to quantify biomechanical mechanisms of the kinetics of clot deformation, stretching and contraction driven by platelet filopodia-fibrin fiber pulling interactions [3,4]. These results provided novel biological insights since filopodia had been thought of previously as performing mostly a sensory function. The biomechanical mechanisms and modeling approach to be described can potentially apply to studying other blood clotting processes as well as to other systems in which cells are embedded in a filamentous network and exert forces on the extracellular matrix modulated by the substrate stiffness.
Bio: Professor Mark Alber earned his Ph.D. in mathematics at the University of Pennsylvania. He held several positions at the University of Notre Dame including most recently Vincent J. Duncan Family Chair in Applied Mathematics. He is currently Distinguished Professor in the Department of Mathematics and Director of the Interdisciplinary Center for Data-Driven Modeling in Biology, University of California, Riverside. Dr. Alber was elected in 2011 Fellow of the American Association for the Advancement of Science (AAAS) and received 2024 US Fulbright Scholar Award (The Netherlands). He is currently a section editor in systems biology of PLoS Computational Biology and member of editorial boards of Bulletin of Mathematical Biology and Journal of the Royal Society Interface.