Biophysical Modeling of Light-Induced Modulation in Membrane Signaling Pathways

Abstract Light-based modulation of membrane signaling is a central tool in optogenetics and photopharmacology, enabling precise control of cellular processes. Despite rapid experimental advances, a quantitative understanding of how temporal illumination patterns interact with intrinsic receptor kinetics to shape signaling remains limited. Here, we develop a deterministic biophysical model describing membrane receptors transitioning among inactive, active, and desensitized states under external light input. Light intensity, duty cycle, and stimulation frequency are included as explicit control parameters. Steady-state analysis, stability assessment, and numerical simulations were performed to characterize responses under continuous and pulsed illumination. Pulsed stimulation outperforms continuous light by enhancing peak activation, reducing desensitization, and exploiting intrinsic recovery dynamics. Frequency-dependent analysis identifies intermediate regimes where signaling is optimized, revealing resonance-like interactions between stimulation and receptor time scales. These results demonstrate that temporal structuring of illumination, rather than total light exposure, is the key determinant of signaling efficiency , highlighting design principles for pulsed and frequency-optimized optical control. The framework is independent of specific optogenetic actuators and can be applied broadly to light-responsive systems, including photopharmacological receptors, GPCR pathways, and synthetic circuits. Overall, this work provides a predictive quantitative tool for rational design of optical stimulation protocols and advances understanding of how biophysical constraints govern membrane signaling dynamics.