Demeersseman, N. | Search bioRxiv

bioRxiv2026

The Role of Smooth Muscle Cell Heterogeneity in Cerebral Autoregulation: A Multi-Scale Physics-Based Modeling Study

Background: Cerebral autoregulation stabilizes cerebral blood flow over a range of cerebral perfusion pressures, but the precise shape of the pressure-flow relationship remains debated. The classical triphasic pressure-flow relationship was recently challenged by experiments demonstrating a quadriphasic response, hypothesized to arise from vessel-size-dependent pressure-diameter responses. We tested this hypothesis and investigated whether these size-dependent responses originate from heterogeneity in smooth muscle cell (SMC) abundance, SMC behavior, or neither. Methods: We developed a computational multi-scale physics-based model of cerebral autoregulation linking SMC activity to vessel-scale diameter regulation and organ-scale blood flow. Four scenarios were evaluated: passive vessels, homogeneous SMC abundance and behavior, heterogeneous SMC abundance, and heterogeneous SMC behavior. Predicted pressure-diameter responses and pressure-flow relationships were compared across scenarios and against experimental observations. Results: In contrast to passive vessels, homogeneous SMC activation produced partial flow stabilization, highlighting the key role of SMCs in autoregulation. However, only heterogeneous SMC behavior reproduced the experimentally observed vessel-size-dependent trends in pressure-diameter responses. This scenario also showed the best agreement with the experimental organ-scale pressure-flow relationship (R-squared = 0.93, nRMSE = 5.96%). Conclusion: The model suggests that vessel-size-dependent SMC behavior underlies vessel-size-dependent pressure-diameter responses and shapes the relationship between cerebral perfusion pressure and cerebral blood flow.

bioengineering↗

bioRxiv2025

Stretching the Limits: From Planar-Biaxial Stress-Stretch to Arterial Pressure-Diameter

Understanding the physiological condition of the vascular system is critical to explain, treat, and manage vascular disease. Numerous experimental and computational studies characterize the mechanical behavior of arterial tissue under controlled laboratory conditions. However, translating this knowledge into physiologically realistic conditions remains challenging. Key difficulties include selecting suitable and relevant test methods, minimizing uncertainty, and ensuring robust model validation. We present a novel integrative approach to translate laboratory experiments on arterial samples into clinically relevant pressure-diameter behavior. We perform controlled planar-biaxial tests on carotid arteries under three stretch ratios and generate axial and circumferential stress-stretch data to calibrate a fiber-reinforced soft tissue model. Using an analytical thick-walled cylindrical model, we predict subject-specific pressure-diameter behavior, informed by arterial prestretches from ring opening experiments. We systematically compare predictions against extension-inflation experiments on tubes from the same artery by applying controlled pairs of axial stretch and inner pressure, while recording outer diameter. We quantify prediction error in absolute and relative stretch regimes and evaluate the importance of the load-free reference dimensions. Results show how planar-biaxial tests probe different stretch regimes compared to extension-inflation deformations, leading to extrapolation of model predictions. We demonstrate how the constitutive material parameters can be fitted to different biomechanical loading conditions and assess the sensitivity of the simulations to axial stretch and circumferential prestretch. Only when key model parameters are accurately captured and their uncertainty propagated, planar-biaxial stress-stretch data can reliably predict arterial pressure-diameter behavior.

bioengineering↗