A General Framework for Closed Loop Negative Feedback Multivariable Physiological Control Systems: Existence, Uniqueness, and Stability of Homeostatic Equilibrium Points

作     者：Procopio, Anna Tedesco, Annarita Regio, Fabrizio Lo Cesarelli, Giuseppe Donisi, Leandro Ricciardi, Carlo Merola, Alessio Ponsiglione, Alfonso Maria Romano, Maria Montefusco, Francesco Cosentino, Carlo Amato, Francesco 

作者机构：Univ Magna Graeciadi Catanzaro Dept Expt & Clin Med I-88100 Catanzaro Italy Univ Naples Federico II Dept Publ Hlth I-80131 Naples Italy Univ Naples Federico II Dept Elect Engn & Informat Technol I-80125 Naples Italy Univ Naples Parthenope Engn Dept Naples Italy Univ Campania Luigi Vanvitelli Dept Adv Med & Surg Sci I-80138 Naples Italy Univ Napoli Parthenope Dept Econ Law Cybersecur & Sports Sci Naples Italy 

出 版 物：《IEEE ACCESS》 (IEEE Access)

年 卷 期：2025年第13卷

页      面：17630-17651页

核心收录：

基　　金：Italian Ministry of University and Research (MUR) - NextGenerationEU: "National Research Centre for High Performance Computing, Big Data and Quantum Computing-ICSC" under Grant National Recovery and Resilience Plan (NRRP) [CN00000013] The "Research and Innovation on Future Telecommunications Systems and Networks-RESTART"NRRP Partenariato Esteso Telecomunicazioni del Futuro (PE14) [CUP E63C22002040007] The "A Multiscale Integrated Approach to the Study of the Nervous System in Health and Disease-MNESYS"NRRP Mission 4, Component 2 (NRRP M4C2) [CUP E63C22002170007] 

主　　题：Physiology Biological system modeling Control systems Biology Negative feedback Regulation Homeostasis Process control Integrated circuit modeling Delays Multivariable physiological control systems neuromuscular stretch reflex cellular growth dynamics stability of homeostatic equilibrium 

摘      要：The study of homeostatic equilibrium is a key concern in several fields, from physiology and biology to medicine and biomedical engineering. Control theory approaches can provide effective strategies to model physiological control systems, helping in understanding the dynamics of bio- and physio-logical regulation processes. However, the intrinsic complexity of living systems makes it difficult to identify unified biomodels that can represent a wide variety of physiological systems. In this context, the present work proposes a general framework to model the dynamics and describe the behavior of a wide class of multivariable physiological control systems, from the molecular to the whole-organ scale. The framework adopts a structure based on a closed-loop topology taking into account multiple inputs and outputs and with the negative feedback action intrinsically embedded within the model. The development of such a general model has at least three important repercussions: the first concerns the possibility of better understanding the basic mechanisms common to many physiological systems;the second is to develop a common theoretical framework to enable effective approaches to the analysis and design of synthetic biological control systems;finally, the investigation of the structural properties of the model in a general context, allows a guided and simplified application to specific cases. To this regard, in this paper, the existence, possible uniqueness and stability properties of the homeostatic equilibrium points of the general model are investigated;the theoretical framework is then illustrated through two real-world case-studies: (i) the PI3K/AKT/mTOR pathway nonlinear dynamics, a critical regulator of cellular growth, proliferation, and survival;(ii) the control mechanism of the neuromuscular stretch reflex, among the prime triggers implicated in postural control. Results proved the capability of the proposed framework to capture the intricate dynamics of multivari