logo : Dynacaps 2023

Dynamics of Capsules, Vesicles and Cells in Flow

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  • Keynote lectures

    Manouk Abkarian

    Université de Montpellier, France

    Title: Transport and mixing of blood suspensions in the microcirculation

    Abstract: In this presentation, I will discuss the role of blood being a dense suspension of highly deformable red blood cells (RBCs) on two problems associated to the microcirculation.

    First at the capillary scale, RBCs have to travel in reticulated networks of tiny vessels forcing the cells to deform in a rich variety of shapes to deliver gases of the respiration as close as possible to the cells of the organism. I will question how the cells interaction with individual nodes of a network contributes to the overall perfusion efficiency of blood. To investigate this network rheology, I will present experiments on the flow of RBCs through uniform networks with varying geometry and topology that show how transport characteristics at the capillary scale are non-linear with the applied peripheral pressure. The flow increases for increasing pressure difference. This non-linearity depends not only on the volume fraction of RBCs but also on the topology of the network. Our first observations show that this is likely correlated to the local behavior of RBCs membrane as they travel through the network.

    In the second part of the presentation, I aim to discuss the importance of blood being a well-mixed fluid at the arterio-venule scale of the microcirculation. Mixing at these small scales is indeed notoriously hard. This property of small-Reynolds-number flows is especially critical to overcome at the scale of the microcirculation in order for blood to transport nutrients and metabolic wastes in a well-mixed state. In vivo observations have shown how RBCs do not mix in vivo and mixing seems limited to pure diffusion. However, granular suspensions are known to present signs of shear-enhanced diffusion which could help mixing for blood suspensions which are however far from model granular systems. Using squared-cross-sectional microchannels, we investigate the mixing of fluorescent macromolecules in a suspension of RBCs with different volume fractions and flow rates around physiological values. Our experiments show that the mixing depends not only on the volume fraction of RBCs but also strongly on the flow rate. Mixing improves at higher flow rates for fixed volume fractions, and we found an optimum that maximizes mixing at the levels of volume fractions found in vivo. These trends are also observed in aggregated RBCs and is prominent in denser suspension. Our results suggest that RBCs not only are oxygen transporter but also help to maintain blood in a well-mixed state in microcirculatory flows. 

    Prosenjit Bagchi

    Rutgers University, USA

    Biosketch: Prosenjit Bagchi is a professor in Mechanical and Aerospace Engineering Department at Rutgers University in New Jersey. He completed undergraduate education in India, and PhD from the University of Illinois at Urbana-Champaign. He joined Rutgers in 2003 after his post-doc at Johns Hopkins University. His research interest is in computational fluid dynamics, and biofluid mechanics. Current projects in his group include high-fidelity modeling of blood flow in the microcirculation, and cellular motility in 3D. He was a recipient of the Andreas Acrivos dissertation award from the American Physical Society, and US National Science Foundation CAREER award. His research has been funded by the National Science Foundation and National Institute of Health

    Title: Cell-resolved modeling of capillary network-scale blood flow

    Abstract: I will present some prior and recent research works considered in my group on computational modeling of microcirculatory blood flow. First, I will present a 3D model of flow of deformable red cell suspension in physiologically realistic and geometrically complex microvascular capillary networks. Results on the influence of cell deformability on capillary network hemodynamics, retinal microvascular network hemodynamics, and tumor microcirculation will be presented. I will then present some of our recent efforts on application of machine learning in predicting capillary network hemodynamics, and on capsule flow through deformable micro-vessels.

    Stephan Gekle

    Bayreuth University, Germany

    Biosketch: Stephan Gekle studied physics at the Universities of Stuttgart (Germany) and Valladolid (Spain). From 20062009 he worked on his PhD thesis on classicial fluid mechanics in the Physics of Fluids group at the University of Twente in the Netherlands. During his PostDoc at TU Munich from 2010 to 2012 his research focus shifted to molecular dynamics of water around biological molecules. In 2013 he received a Lichtenberg Assistant Professorship with which he started his own research group at the University of Bayreuth in Germany. In 2018 he was tenured at the same university.

    His research focus is on the biophysics and biomechanics of living cells in hydrodynamic flows. This includes cells in the blood circulation, but also artificial flows such as those occuring during the 3D printing of cell-laden bioinks. Being a theoretical physicist, he uses both mathematical-analytical modeling and large-scale computer simulations in close collaboration with experimental partners.

    Title: Transient behavior of simple and not-so-simple cells in blood flow

    Abstract: Red blood cells are the most abundant cell type in mammals. Their interior is entirely filled with a liquid hemoglobin solution which is enclosed by a thin elastic membrane. Despite their physical simplicity, red blood cells exhibit extremely rich and fascinating dynamics when flowing through our blood vessels. In the first part of this talk, I will show some examples of these dynamics and how they can be physically understood by using computer simulations.

    In the second part, I will consider a biologically more complex process, namely the formation of blood platelets. A healthy human body produces more than one million platelets per second. While numerous experiments have shown that this highly efficient process of platelet formation is intimately connected to the flowing environment, the precise mechanism is still not understood. Here, I will present some hypothesis how platelet formation can be viewed analogously to the breakup of a liquid jet in the classical Rayleigh-Plateau instability.

    Anne Juel

    Manchester University, UK

    Biosketch: Anne Juel is Professor of Fluid Mechanics at the University of Manchester and has been the Director of the Manchester Centre for Nonlinear Dynamics since 2014. She obtained her D.Phil from Oxford University in 1998 and was a post-doctoral fellow at UT Austin and Manchester before her appointment to a faculty position at the University of Manchester in 2001. Her research focuses on fluid-structure interaction, interfacial instabilities, wetting, yield phenomena and biomimetic microfluidic models. She was elected to a Fellowship of the American Physical Society in 2019. She is an asso­ciate editor of JFM and serves on the editorial boards of Annual Review of Fluid Mechanics and PRSA. She is currently chair of the Division of Fluid Dynamics of the American Physical Society.

    Title: Microfluidic model of haemodynamics in porous media

    Abstract: The human placenta relies on well-orchestrated haemodynamics to deliver its multiple functions. Its geometrical complexity and lack of appropriate animal models mean that laboratory models offer a powerful tool to investigate haemodynamics and haemorheology in the human placenta and other complex biological tissues. We develop a model of red blood cells (RBCs) with polydimethylsiloxane capsules of adjustable diameter and membrane thickness, which are microfabricated using a 3D nested glass capillary device. The elastic modulus of the membrane can be varied by an order of magnitude by adjusting the chemistry and the capsules are further deflated by osmosis to match the surface-area-to-volume ratio of real RBCs. We start by testing the capacity of our capsules to mimic the motion and large deformations of suspensions of RBCs in simple conduits. We then characterise capsule suspension flows in porous media of increasing complexity in terms of the dynamic distribution of particles and flow resistance as functions of haematocrit, disorder of the medium and capillary number.

    Tim Pedley

    Cambridge University, UK


    Tim Pedley, FRS, is Emeritus G I Taylor Professor of Fluid Mechanics in the Department of Applied Mathematics and Theoretical Physics (DAMTP) in the University of Cambridge. He was Head of DAMTP from 2000 to 2005 and co-Editor of the Journal of Fluid Mechanics from 2000 to 2006, having been an Asso­ciate Editor since 1983. Since 1968, his research is in the application of fluid mechanics to phenomena in biology and medicine. After having started exclusively in internal, physiological, fluid dynamics (airflow in the lungs, blood flow in arteries and veins), he then worked more on the interaction of living organisms with their fluid environment, notably fish swimming and the collective behaviour of swimming micro-organisms.

    He had the honor to be elected Fellow of the Royal Society (1995), Foreign Asso­ciate of the US National Academy of Engineering (1999), Fellow of the American Institute of Medical and Biological Engineering (2001), Fellow of the American Physical Society (2005), Foreign Fellow of the National Academy of Sciences, India (2007), Chair of the World Council for Biomechanics (20026), President of the International Union of Theoretical and Applied Mechanics (200812), and Member of the Academia Europaea (2011). He was awarded the Gold Medal of the IMA in 2008.

    Title: A glimpse of Dominique Barthès Biesel’s career, from a dear friend and colleague

    Petia Vlahovska

    Northwestern University, USA

    Biosketch: Petia M. Vlahovska received a PhD in chemical engineering from Yale (2003) and MS in chemistry from Sofia University, Bulgaria (1994). She was a postdoctoral fellow in the Membrane Biophysics Lab at the Max Planck Institute of Colloids and Interfaces (Germany) and spent ten years on the faculty at Dartmouth College and Brown University, before joining the faculty at Northwestern University in 2017. Her research is in fluid dynamics, membrane biophysics, and soft matter. Prof. Vlahovska is the recipient of David Crighton Fellowship (2005), NSF CAREER Award (2009) and a Humboldt Fellowship (2016). In 2019, she was elected fellow of the American Physical Society.

    Title: Role of membrane viscosity in the dynamics of vesicles and capsules

    Abstract: Lipid bilayers are the main structural component of the membranes that envelope cells and cellular organelles. The nanometrically thin bilayer behaves as a two-dimensional fluid and its shear viscosity controls mobility of embedded biomolecules and membrane remodeling. In this talk, I will overview our recent theoretical and experimental work on quantifying membrane viscosity and its effects on membrane dynamics, in particular, the thermally-driven membrane undulations and vesicle deformation in an applied uniform electric field [1,2]

    [1] Faizi et al. Biophys. J. 121:910918 (2022)

    [2] Faizi et al, arXiv:2208.07966 (2022)

    Yi Sui

    Queen Mary University of London, UK

    Biosketch: Dr Yi Sui is Professor in Fluid Mechanics and Director of Research in the School of Engineering and Materials Science at the Queen Mary University of London (QMUL). He received his first degree from the University of Science and Technology of China in 2004, PhD from the National University of Singapore (NUS) in 2008, and then got postdoctoral training at the NUS and Imperial College London between 20092011, before joining the faculty of QMUL in 2012. Dr Sui’s research interests are mainly in the areas complex flow systems, e.g., those involve suspending microcapsules and biological cells, multiphase flows, moving contact lines. He has published 50+ papers in leading journals such as the Annual Review of Fluid Mechanics, Journal of Fluid Mechanics, Journal of Computational Physics, and those publications have attracted about 3000 citations. Dr Sui’s recent research efforts have been focused on modelling and characterisation of suspended cancer cells.

    Title: A computational model for the transit of cancer cells through a constricted microchannel

    Abstract: The dynamics of cancer cells flowing in microchannels is a fundamental problem that lies in the heart of numerous biomedical applications. In this talk, I will summarise our recent work concerning the development of a three-dimensional computational framework to simulate the transient deformation of suspended cancer cells flowing through a constricted microchannel. We model cancer cells as a liquid droplet enclosed by a viscoelastic membrane, and its nucleus as a smaller stiffer capsule. The cell deformation and its interaction with the suspending fluid are solved through an immersed boundary lattice Boltzmann method. To identify a minimal mechanical model that can quantitatively predict the cell deformation, we conduct extensive parametric studies of the effects of the rheology of the cell membrane, cytoplasm and nucleus, and compare the results with a recent experiment conducted on human leukaemia cells. We find that the classical Skalak’s law can accurately predict the steady deformation of the cancer cell in the straight channel, however, for cell transient deformation in the constriction region, excellent agreement with the experiment can only be achieved by employing a viscoelastic cell membrane model with the membrane viscosity depending on its mode of deformation (shear versus elongation). The cell nucleus limits the overall deformation of the whole cell, and its effect increases with the nucleus size. The proposed computational model will be varied on different types of cancer cells in our future work. It has the potential to serve as a general model to guide the design of microfluidic devices to sort cancer cells, or to inversely infer cell mechanical properties from their flow-induced deformation.