Biophysical mechanisms of endothelial cell alignment in blood flow

• Applicant: Professor Dr. Stephan Gekle
• Subject Area: Statistical Physics, Nonlinear Dynamics, Complex Systems, Soft and Fluid Matter, Biological Physics ; Biophysics
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 546825574

Endothelial cells (ECs) form the inner wall of blood vessels. In this location, their upper (luminal) side is permanently exposed to blood flow. To deal with and to benefit from this situation, ECs have developed an astonishing capability of adaptation. After flow exposure, they adapt an elongated shape and form thin actin structures - stress fibers - which align with the flow direction and anchor the cell to the extracellular matrix on the bottom side. Failure of ECs to properly align with the flow is known to cause chronic inflammation and is a major risk factor for atherosclerosis. Despite intensive research efforts, the biophysical mechanism behind flow sensing and flow alignment in ECs is presently not understood. Here, we will develop and use a series of successively more complex computational models to tackle this problem. Our starting point will be the model developed by Deshpande, McMeeking & Evans (Proc. Nat. Acad. Sci. (USA) 2006) which explains stress fiber formation in static, adherent cells, but has thus far not been coupled to hydrodynamic flows. We will implement this model first in two and later in three dimensions. The key extension will be a full two-way coupling between the DME model and a hydrodynamic flow solver based on the boundary-integral method. With this we aim to provide a deeper understanding of the biophysical mechanism behind stress fiber formation and alignment in endothelial cells. To calibrate our model parameters based on experimental data, we will use modern statistical tools such as Bayesian Inference and collaborate closely with the experimental group of Abdul Barakat, École Polytechnique, Paris. Besides providing high-quality experimental data, the cooperation with the Barakat group will also pave the way towards application of our results for new explanations of atherosclerosis and to improved designs of vascular stents.

• DFG Programme: Research Grants