Feedback Control in Cellular Mechanoregulation: A Model of Caveolar Dynamics
Conference
Kazemi, M, Gal, CG, Baum, TE et al. (2025). Feedback Control in Cellular Mechanoregulation: A Model of Caveolar Dynamics
. 4803-4808. 10.1109/CDC57313.2025.11312800
Kazemi, M, Gal, CG, Baum, TE et al. (2025). Feedback Control in Cellular Mechanoregulation: A Model of Caveolar Dynamics
. 4803-4808. 10.1109/CDC57313.2025.11312800
Cells live in a mechanically rich environment. Mechanical stimuli from outside the cell (e.g., shear stress due to fluid flow, stretching due to forces from neighboring cells, etc.) have a profound effect on cells' internal state. This is potentially because cells need to adapt to their mechanical environment to ensure the integrity of the plasma membrane (PM). As such, at the heart of the cellular mechanoregulation problem, there lies an optimal control problem: how cells can observe and control their mechanical environment. Previous experimental work has shown that cells can observe the stretching of the PM through specialized PM domains named caveolae (cave-like invaginations on the PM composed of two main proteins: cavin and caveolin). Caveolae play a dual role in cellular mechanoregulation. First, they can act as observers of PM's mechanical state by flattening in response to forces, triggering downstream signaling pathways. Second, they can act as actuators by buffering PM's tension as a result of their flattening in response to forces. Despite experimental evidence indicating implication of caveolae in cellular mechanoregulation, to the best of our knowledge, no control-theoretic analysis of caveolar dynamics in the context of mechanoregulation has been done. As such, we aim to model and analyze the role of feedback in caveolae-dependent mechanoregulation. We construct a novel model of caveolae-dependent signaling highlighting the role of feedback in mechanoregulation. We then demonstrate robustness properties of our model to stochastic perturbations and external mechanical stimuli. Further, we demonstrate through simulations how cells can adapt to their mechanical environment emphasizing the role of caveolae. We also provide an explanation for how our model can explain previous experimental results on the role of caveolins in mechanoregulatory signaling pathways. Overall, we present a novel model of cellular caveolae-dependent mechnoregulation and provide a detailed control-theoretic analysis of how our model can explain experimental data.
