The chapter discusses the mechanisms by which cells sense and regulate the mechanical properties of the extracellular matrix (ECM) to maintain homeostasis in soft connective tissues. Key players in this process include integrins, actomyosin, and ECM constituents like collagens and elastin. Cells use integrins to bind to the ECM and transduce mechanical signals into intracellular responses, while actomyosin transmits and amplifies these signals. The ECM's mechanical properties, such as stiffness and elasticity, influence cell behavior, including migration, proliferation, and differentiation. The chapter highlights the importance of negative feedback mechanisms in maintaining tissue health and the role of mechanical loading rates in ECM turnover and composition. It also explores the molecular mechanisms of mechanotransduction, such as the unfolding of protein domains under force and the role of Rho GTPases in cytoskeletal responses. The chapter concludes by emphasizing the need to understand the regulatory pathways and factors that govern the switch between homeostatic and fibrotic states to develop effective treatments for diseases like fibrosis.The chapter discusses the mechanisms by which cells sense and regulate the mechanical properties of the extracellular matrix (ECM) to maintain homeostasis in soft connective tissues. Key players in this process include integrins, actomyosin, and ECM constituents like collagens and elastin. Cells use integrins to bind to the ECM and transduce mechanical signals into intracellular responses, while actomyosin transmits and amplifies these signals. The ECM's mechanical properties, such as stiffness and elasticity, influence cell behavior, including migration, proliferation, and differentiation. The chapter highlights the importance of negative feedback mechanisms in maintaining tissue health and the role of mechanical loading rates in ECM turnover and composition. It also explores the molecular mechanisms of mechanotransduction, such as the unfolding of protein domains under force and the role of Rho GTPases in cytoskeletal responses. The chapter concludes by emphasizing the need to understand the regulatory pathways and factors that govern the switch between homeostatic and fibrotic states to develop effective treatments for diseases like fibrosis.