Person: Fai, Thomas
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Fai
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Fai, Thomas
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Publication Quantitative biology: where modern biology meets physical sciences(The American Society for Cell Biology, 2014) Shekhar, Shashank; Zhu, Lian; Mazutis, Linas; Sgro, Allyson E.; Fai, Thomas; Podolski, MarijaQuantitative methods and approaches have been playing an increasingly important role in cell biology in recent years. They involve making accurate measurements to test a predefined hypothesis in order to compare experimental data with predictions generated by theoretical models, an approach that has benefited physicists for decades. Building quantitative models in experimental biology not only has led to discoveries of counterintuitive phenomena but has also opened up novel research directions. To make the biological sciences more quantitative, we believe a two-pronged approach needs to be taken. First, graduate training needs to be revamped to ensure biology students are adequately trained in physical and mathematical sciences and vice versa. Second, students of both the biological and the physical sciences need to be provided adequate opportunities for hands-on engagement with the methods and approaches necessary to be able to work at the intersection of the biological and physical sciences. We present the annual Physiology Course organized at the Marine Biological Laboratory (Woods Hole, MA) as a case study for a hands-on training program that gives young scientists the opportunity not only to acquire the tools of quantitative biology but also to develop the necessary thought processes that will enable them to bridge the gap between these disciplines.Publication Image-based model of the spectrin cytoskeleton for red blood cell simulation(Public Library of Science, 2017) Fai, Thomas; Leo-Macias, Alejandra; Stokes, David L.; Peskin, Charles S.We simulate deformable red blood cells in the microcirculation using the immersed boundary method with a cytoskeletal model that incorporates structural details revealed by tomographic images. The elasticity of red blood cells is known to be supplied by both their lipid bilayer membranes, which resist bending and local changes in area, and their cytoskeletons, which resist in-plane shear. The cytoskeleton consists of spectrin tetramers that are tethered to the lipid bilayer by ankyrin and by actin-based junctional complexes. We model the cytoskeleton as a random geometric graph, with nodes corresponding to junctional complexes and with edges corresponding to spectrin tetramers such that the edge lengths are given by the end-to-end distances between nodes. The statistical properties of this graph are based on distributions gathered from three-dimensional tomographic images of the cytoskeleton by a segmentation algorithm. We show that the elastic response of our model cytoskeleton, in which the spectrin polymers are treated as entropic springs, is in good agreement with the experimentally measured shear modulus. By simulating red blood cells in flow with the immersed boundary method, we compare this discrete cytoskeletal model to an existing continuum model and predict the extent to which dynamic spectrin network connectivity can protect against failure in the case of a red cell subjected to an applied strain. The methods presented here could form the basis of disease- and patient-specific computational studies of hereditary diseases affecting the red cell cytoskeleton.Publication Active Elastohydrodynamics of Vesicles in Narrow Blind Constrictions(American Physical Society (APS), 2017-11-10) Fai, Thomas; Kusters, R.; Harting, John; Rycroft, ChristopherFluid-resistance limited transport of vesicles through narrow constrictions is a recurring theme in many biological and engineering applications. Inspired by the motor-driven movement of soft membrane-bound vesicles into closed neuronal dendritic spines, here we study this problem using a combination of passive three-dimensional simulations and a simplified semianalytical theory for the active transport of vesicles forced through constrictions by molecular motors. We show that the motion of these objects is characterized by two dimensionless quantities related to the geometry and to the strength of forcing relative to the vesicle elasticity. We use numerical simulations to characterize the transit time for a vesicle forced by fluid pressure through a constriction in a channel and find that relative to an open channel, transport into a blind end leads to the formation of a smaller forward-flowing lubrication layer that strongly impedes motion. When the fluid pressure forcing is complemented by forces due to molecular motors that are responsible for vesicle trafficking into dendritic spines, we find that the competition between motor forcing and fluid drag results in multistable dynamics reminiscent of the real system. Our study highlights the role of nonlocal hydrodynamic effects in determining the kinetics of vesicular transport in constricted geometries.Publication Lubricated Immersed Boundary Method in Two Dimensions(Elsevier BV, 2018-03) Fai, Thomas; Rycroft, ChristopherMany biological examples of fluid–structure interaction, including the transit of red blood cells through the narrow slits in the spleen and the intracellular trafficking of vesicles into dendritic spines, involve the near-contact of elastic structures separated by thin layers of fluid. Motivated by such problems, we introduce an immersed boundary method that uses elements of lubrication theory to resolve thin fluid layers between immersed boundaries. We demonstrate 2nd-order accurate convergence for simple two-dimensional flows with known exact solutions to showcase the increased accuracy of this method compared to the standard immersed boundary method. Motivated by the phenomenon of wall-induced migration, we apply the lubricated immersed boundary method to simulate an elastic vesicle near a wall in shear flow. We also simulate the dynamics of a vesicle traveling through a narrow channel and observe the ability of the lubricated method to capture the vesicle motion on relatively coarse fluid grids.