Purpose <p>Modeling eukaryotic cell flow in microfluidic devices and capillary networks can be instrumental in assessing how cell mechanics influence its behavior. Due to the viscoelastic characteristics of cells and their capacity for substantial deformation, models that are both detailed and computationally efficient are necessary to explore cell rheology. We present a coarse-grained model for simulating the mechanics of eukaryotic cells in flow, with a focus on the modeling of cell membrane, nucleus, and cytoskeleton.</p> Methods <p>The cell and nucleus membranes are represented using surface triangulation, capturing both viscous and elastic properties of the membranes. To maintain computational efficiency while retaining the ability to reproduce the viscoelastic behavior of the entire cell, the complexity of the cytoskeleton model is reduced through the use of the viscoelastic bonds. Dissipative Particle Dynamics is employed to facilitate flow simulations; however, the model is suitable for use in many existing continuum and particle-based methods.</p> Results <p>The cell model is calibrated and validated using experimental data from micropipette aspiration and microfluidic experiments involving breast epithelial cells (MCF-10A).</p> Conclusion <p>We believe the balance between simplicity and accuracy makes the proposed model a valuable tool for simulating eukaryotic cell mechanics in flow, enabling faster simulations, while also simplifying the parameterization procedure.</p>