In multicellular organisms, cells proliferate within a confined space, facing a spatial constraint that impacts their ability to expand. As confined cells grow, the continuous biosynthesis still occurs while cell expansion is limited. This results in an increase in intracellular crowding, defined as the accumulation of macromolecules such as proteins, nucleic acids within the cytoplasm. In yeasts, macromolecular crowding driven by mechanical pressure relates to biomass production reduction, further leading to growth reduction. This biophysical feedback might be essential for a physiologically-controlled multicellular proliferation, avoiding over-proliferation. In solid cancer the rapid tumor growth and the environment remodeling explain their high intensity of compressive forces. One example is pancreatic ductal adenocarcinoma (PDAC) where mechanical pressure induced-macromolecular crowding interferes with multicellular aggregates growth and cell cycle progression, potentially leading to a mechanical form of chemotherapeutic resistance. Investigating how cells adapt to mechanical stress in controlled experimental conditions can therefore provide fundamental insight into how compression contributes to growth regulation in physiologically and pathologically relevant settings.